CA2142647A1 - Fungicide 2-imidazoline-5-ones derivatives - Google Patents

Abstract

The invention relates to 2-imidazoline-5-ones derivatives, of general formula (I): <IMG> in which: - R1 is H, or a vinyl or allyl group, or an alkyl or haloalkyl radical, -n = Or 1; Y is O or S; - R2 is an alkyl or haloalkyl group, or the cyclopropyl group; - R3 is an aryl or heteroaryl radical, optionally substituted, comprising in particular phenyl, naphthyl, - R4 is a hydrogen atom and various radicals including a formyl or aroyl radical, an acyl radical of 2 to 6 carbon atoms, - R5 is in particular H or the hydroxy, mercapto, nitro, cyano, thiocyanato or azido group; or an optionally substituted alkyl or cycloalkyl radical, -W is O, S or SO; - Ar1 is a divalent radical, optionally substituted, which derives from a radicalaryl or heteroaryl comprising, in particular, the phenyl, naphthyl, thienyl radicals, - Ar2 is a mono or bicyclic system of 5 to 10 atoms, optionally substituted, which is aromatic , saturated or unsaturated, and which is either a carbocyclic system or a heterocyclic system containing from 1 to 4 heteroatoms chosen from O, S, or N, - X is especially -C (O) NH-, -NHC (O) NH -, -SO2NH-, -CH2O-, -CH2NH-, CH2-. The invention also relates to the preparation of these compounds and their use as a broad spectrum fungicide.

Description

21 ~ 2647 2-Imidazoline-5-ones derivatives ~ ongicides.

The present invention relates to new compounds with a group

2-irnidazoline-5-one for phytosanitary use. It also concerns processes for the preparation of said compounds and optionally the products usable as illlelmediaries in the preparation processes. She finally, e the fungicidal compositions based on these compounds and the methods for controlling fungal diseases of crops using these compounds.

We know of 2-imidazoline-5-ones for phytosanitary use by e.llopéell patent application EP 0 551048 and by international applications WO 93/24467 and WO 94/01410.

An object of the pr ~ senle invention is to provide new compounds colllpolLanl a 2-imidazoline-5-one group preselllant plo ~ improved riies in the treatment of fungal diseases of cultures.
Another object of the present invention is to provide compounds pl ~ se, llant a spectrum of use also improved in the field of fungal diseases, notalllll, enl for the treatment of fungal diseases of rice 2s and for the treatment of brown wheat rust.

It has now been found that these goals can be achieved, by in whole or in part, by means of the products of the invention, described below.

The subject of the invention is first of all compounds which are 2-unidazoline-5-ones derivatives of general formula (I):

21 ~ 647 RII ~ T q ~ Y) n --R 2 Ar 2 - X - Ar I ~ N `N ~ R 3 in which:

- Rl l ~ p, ~ senle a hydrogen atom, or a vinyl or allyl group, or a alkyl or haloalkyl radical, each of 1 to 3 carbon atoms;
or, Rl and Ar2-X-Arl can also form, with the carbon to which they are linked on the imidazolinone cycle, the following motif:
(& H2) m ~

Ar2--in which the point in bold type l ~ p, is the call, one of the imidazolinone cycle of formula (I) to which the radicals Rl and Ar2-X-Arl are linked, and m equals 2, 3 or 4;
-n = Where l;

- Y le, l, le3enle the oxygen or sulfur atom;

- R2 lepl ~ sehle:
- the hydrogen atom when n equals 0 or - an alkyl or haloalkyl group, each of 1 to 3 carbon atoms or cyclopropyl group;

- R3 l ~ presellte an aryl or heteroaryl radical co ~ nplellant phenyl, naphthyl, pyridyle, pyrirnidyle, pyridazinyle, pyrazinyle, thiazolyle, benzothienyle, benzofuryl, quinolinyl, isoquinolinyl, benzothiazolyl or methylene dioxyphenyl, each of these radicals being optionally substituted with 1 to 7 21 i25'17 gloupell-enls, preferably from 1 to 3 groupenleJ) Is, chosen from among meanings of Rs defined below;

- R4 re ~ - ~ senle a hydrogen atom, a formyl or aroyl radical, a radical s acyl of 2 to 6 carbon atoms, an alkoxycarbonyl radical of 2 to 6 atoms of carbon, an aryloxycarbonyl or arylsulfonyl radical, a radical alkylsulfonyl of 1 to 6 carbon atoms, or an alkyloxalyl radical or alkoxyoxalyl of 3 to 6 carbon atoms;

- ~ 5 ~ s ~
-a halogen atom or the hydroxy group, nle, ~ a ~ to, nitro, SFs, cyano, thiocyanato or azido; or an alkyl, haloalkyl, cyanoalkyl, alkoxy, haloallcoxy radical, cyanoalkoxy, alkylthio, haloalkylthio, cyanoalkylthio, alkylsulfinyle, s alkylsulfonyl, haloalkylsulfinyl or haloalkylsulfonyl, each from 1 to 6 carbon atoms; or a cycloalkyl, halocycloalkyl, alkenyl, alkynyl, alkenyloxy radical, alkynyloxy, alkenylthio, alkynylthio, each of 3 to 6 call atoms, olle ; or an amino radical optionally mono or disubstituted by a radical allcyl or acyl of 1 to 6 carbon atoms or alkoxycarbonyl of 2 to 6 carbon atoms; or - an alkoxycarbonyl group of 2 to 7 carbon atoms; or - an N-alkylcarbamoyl group of 2 to 7 carbon atoms; or 2s - an N, N-dialkylcarbamoyl group of 3 to 13 carbon atoms;
.
- W lep ~: se ~ lle O, S or SO;

- Arl is a divalent radical which derives from an aryl or heteroaryl radical including phenyl, naphthyl, thienyl, fi ~ ryle, pyrrolyle, pyridyle radicals, benzothienyl, benzofuryl, indolyl, quinolinyl, isoquinolinyl, or methylenedio ~ yphél, yle, each of these radicals being optionally substituted by 1 to 6 gl ~ upel, lcnls, preferably by 1 to 3 groups, chosen parrni lessignifications of Rs;

21 ~ 2 ~ 7 - Ar2 repl ~ se. ~ Le a mono or bicyclic system of 5 to 10 atoms, which is aromatic, saturated or unsaturated, and which is either a carbocyclic system or a heterocyclic system containing from 1 to 4 heteroatoms chosen from 0, S, or N, and which colllplelld the phenyl, naphthyl, dihydronaphthyl radicals, s tetrahydronaphthyl, thienyl, furyl, pyrrolyl, pyridyl, benzothienyl, benzofuryl, indanyl, indolyl, quinolinyl, isoquinolinyl, methylenedio ~ yl) hényle, ilnidazolyle, pyrazolyle, triazolyle, oxazolyle, isoxazolyle, thiazolyle, isothiazolyle, oxadiazolyle, thiadiazolyle, benzilllidazolyle, indazolyle, benzoxazolyle, benzisoxazolyle, benzothiazolyle, o benzisothiazolyle, pyrimidyle, pyrazinyle, pyridazinyle, triazinyle, naphtyridyle, quinoxazolyl, quinazolyl, cinnolyl or phthalazinyl, each of these radicals being optionally substituted by 1 to 7 groupen, ellts, preferably by 1 to

3 groupel., Enls, chosen from the meanings of R5;

- X lepl ~ sellle a sequence of general formula:

(R ") j - A - (R) k in which:
- j and k, identical or different, are equal to 0 or 1;
- R "and R ', identical or different, leplresentelll a chain hydrocarbon, saturated or unsaturated, which contains from 1 to 6 atoms of carbon, optionally substituted with 1 to 12 groupen.e.lls, of preferably by 1 to 3 gloupelllellts, chosen from R7 defined above 2s after; and in which one or more carbon atoms may be replaced by 0, S, N (Ro), Ror being defined below;
- Has the present 0, S, N (R6), S0, S02, C0, CS ,, Si (R8) (R 8) ~ N2.
C (Rlo) (R 10) ~ or - ~ N ~ S or ~ ' or ~
in which Z le ~) les ~ e 0, S, C (RI l) (R 1 1); R8 to Rl I being defined below;

21 ~ 2 ~ 47 epl ents:
- a hydrogen atom or a cyano, hydroxy group, amino, formyl, morpholino, piperidino, pyrrolidino, s piperazino, or - an alkyl, haloalkyl, cyanoallcyl, alkoxy radical, haloalkoxy, cyanoalkoxy, alkylsulfonyl, haloalkylsulfonyl, cyanoalkylsulfonyl, each co. ~ ant from 1 to 6 carbon atoms, or lo - a monoalkylamino or dialkylamino radical, or - a cycloalkyl, halocycloalkyl, alkenyl radical, alkynyl, alkenyloxy, alkynyloxy, each 3 to 6 atoms of carbon; or - an acyl or alkoxycarbonyl radical, each from 2 to 6 carbon atoms; or - a carbamoyl radical (optionally substituted by a or two alkyl radicals) of 1 to 7 carbon atoms or sulfamoyl of 1 to 6 carbon atoms; or - an aroyl or arylsulfonyl radical; or - an alkyloxalyl or alkoxyoxalyl radical, each from 3 to 8 carbon atoms; or - an oxamyl radical (optionally substituted by one or two alkyl radicals) with 2 to 8 catbone atoms - R7 represents a halogen atom, a cyano group, thiocyanato, hydroxycarbonyl, amino (optionally substituted), hydroxyl, oxo, alkoxy, alkoxycarbonyl, haloalkoxy, alkoxyalkoxy, thiol, alkylthio, haloalkylthio, alkoxyalkylthio, acyloxy, alkyl, haloalkyle, alkoxyalkyle, alkylidene, aroyloxy, heteroaroyloxy, arylacyloxy, cycloalkylcarbonyloxy, acylthio, aroylthio, heteroaroylthio, arylacylthio, cycloalkylcarbonylthio, carbamoyloxy (optionally substituted), carbamoylthio (optionally substituted), thiocarbamoyloxy (optionally substituted), dithiocarbamoyl (optionally substituted), acylamino, cycloalkylcarbonylarnino, aroylamino, ureïdo 21 12 ~ 7 \

(optionally substituted), thiouréïdo, alkoxycarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, aminosulfonylamino (optionally substituted), it being understood than:
s - optionally substituted means radicals possibly sul ~ slil ~ és by one or two alkyl radicals, - each aliphatic hydrocarbon radical has from 1 to 4 carbon atoms, and - the cycloalkyl radical contains from 3 to 7 atoms of c ~ ll, o ~

- R8 and R'8, identical or different, Icpléselllent:
- an alkyl radical of 1 to 6 carbon atoms; or - a cycloalkyl radical of 3 to 7 carbon atoms; or - an alkenyl, alkynyl tadical of 2 to 6 atoms of carbon; or - an arylalkyl radical, of benzyl pteference, or a optionally substituted aryl radical, preferably phenyl optionally substituted with 1 to 5 gluupel ~ lellls, preferably by 1 to 3 gl ~ u ~) enle .. ~ s, chosen from meanings of R5;

- Rg leprésellle:
- the hydrogen atom, or a morpholino group, piperidino, pyrrolidino, l) ip ~ razino; or - an alkyl, haloalkyl, cyanoalkyl, alkoxy radical, haloalkoxy, cyanoalkoxy, alkylthio, haloalkylthio, cyanoalkylthio, each of 1 to 6 carbon atoms or dialkylamino containing from 2 to 6 carbon atoms;
- Rlo and R 1O, identical or different, lep ~ es ~ nlent the atom of hydlogelle or an alkoxy group containing 1 3 6 atoms of carbon or R7;

`2 ~ 42 ~ 47 - Rll and R 11, identical or different, lepl; feel the atom hydrogen or halogen or an alkyl group of 1 to 3 atoms of c &lbolle;

as well as the salified forms, and the enantiomers and stereoisomers of these compounds, notalllll, el ~ the 2 enantiomers of each of these compounds which correspond to the asymmetric carbon of the imidazolinone ring carrying R1;

o and with the exception of compounds for which:
- when (Y) n-R2 leplésellle a methylthio, a methyl or an ethyl, Ar2-X-Arl le ~ esellle a phenoxyphenyl group, optionally substituted;
- when (Y) n-R2 ~ eplese ~ a methoxy, when Rl is methyl, when R3 l ~ resellle a phenyl or pyridyl radical, optionally substituted by a fluorine atom or a methyl group, when R4 is hydrogen, and when W leplésenle an oxygen atom, then Ar2-X-Arl leplésenle is a 4-phenoxyl, hényl group, optionally substituted on its phenoxy part by 1 or 2 fluorine atoms, namely the 3-phenoxyphenyl group;

and with the exception of the compound of formula:
C ~ 3 N ~ / sc ~ 3 [~ CH2O / [~ --N` Nl l ~

In the present text, the generic terms alkyl, acyl, and aroyl, have 2s the following meanings:
- alkyl means a linear or branched aliphatic radical;
- acyle means:
- an alkylcarbonyl or haloalkylcarbonyl group; or - an alkoxyalkylcarbonyl or alkylthioalkylcarbonyl group; or - an alkenylcarbonyl group; or - an alkynylcarbonyl group; or - a cycloalkylcarbonyl or halocycloalkylcarbonyl group;

2 1 4 ~ ~ ~ J

- aroyl means an arylcarbonyl group, the aryl group having the same meanings as those indicated as preferred for Ar2, and being optionally substituted by R5.

The compounds of formula (I) are preferred in which:
- ~ r ~ presents ~ a divalent radical derived from a phenyl, naphthyl, thienyl, pyridyle, bel ~ ollliényle, quinolinyle, each of these radicals being optionally substituted with 1 to 3 ~ luul ~ elllents, chosen from the meanings of Rs;
- Ar ~ Icplésellle a phenyl, naphthyl, thienyl, pyridyle radical, bel ~ uthienyl, thiazolyle, belkot ~ liazolyle, pyrhllidyle, each of these radicals being optionally substituted by 1 to 3 groups, chosen from meanings of Rs.

Particularly preferred are the compounds of formula (I) in which:
- Arl l ~ plesellle a divalent radical derived from a phenyl, thienyl, pyridyle, optionally substituted by 1 to 3 gloupelllents chosen by one halogen atom, an alkyl or haloalkyl radical;
- Ar2 ~ el) resell a phenyl, naphthyl, pyridyl radical, bel ~ utlliazolyle, optionally substituted by 1 to 3 groupelllellls chosen from a halogen atom, an alkyl or haloalkyl radical;
- X le ~ se, lle the sequence of general formula indicated 2s precedes ~ llellt in which:
- - R "and R ', identical or different, represent a chain carbonaceous of 1 to 3 carbon atoms, preferably a methylene group, in which a carbon atom is optionally replaced by O or NH, and which is optionally substituted with 1 to 3 glollpell ~ s chosen from an atom halogen, hydroxyl, oxo or C1-C3 alkyl radical;
- A is O, S, SO, SO2, CO, C (RIo) (R '10), 7107 ~ o ~ Rlo R ~ lo 'or / ~
z wherein:

2 ~ & 4 '7 - Rlo and R'lo, identical or different, are a hydrogen atom, halogen, a hydroxyl radical, Cl-C3 alkyl or Cl-C3 alkoxy;
- Z repl ~ sellle O or C (RI l) (R 11) ~ where Rl I and R '11, identical or are a hydrogen or chlorine atom.

Finally, particularly advantageous compounds are obtained by choosing derivatives of formula I in which simultaneously:
- Rl is a methyl radical;
- R2 is a methyl or ethyl radical;
o - R3 replésenle a phenyl or pyridyl radical;
- R4 is a hydrogen atom or a formyl radical;
- Rs is a halogen atom or a C1-C3 alkyl or C1-C3 radical haloalkyl; and - W is an oxygen atom The compounds of formula (I) are plpalés according to the methods explained below. All the gluu ~ es appearing in the chemical formulas which follow, and already defined in the general formula (I), retain the same meaning, for as far as not specified in ~ lenlelll In the general descli ~ tion of processes for the preparation of the compounds of formula (I), the conditions given are those which are generally used: pl ~ cise that conditions other than those specified may be used, d ~ pelldanl by example of the particular reagents used The structures of all the ploduils which illustrate these processes were established by at least 1 of the following spectral techniques: sl, proton NMR eclolletry, s ~ ec ~ lun.étrie NMR of carbon 13, s ~ ectloll- ~ sort infrared and ~ ecllun ~ étrie massive In the tables which collect these products, indicating the meanings groups of the general formula, methyl, ethyl, propyl, pyridyl, pyrimidinyl, acetyl, phenyl and benzyl are respectively ~ pltsenlés by Me, Et, Pr, Py, Pyrim, Ac, Ph and Bn, and PF means point of fusion (PF) 21 ~ 26 1 ~

The compounds of formula (I), for which Rq is different from the atom of hydrogen, are prepared from the compounds of formula Ia by reaction with a compound of formula R4L ', in the presence of a base and in a solvent medium, according to the following reaction scheme:
s RIN ~ Y) n R2 R4L ~ RI Nq ~ (Y) n - R2 Ar ~ --X - Arl> ~~ `NH - R3 Ar2 - X-- ~ rl ~~ N ~ N ~ R3 (the) (I) In this diagram:
e ~ l ~ sellle the formyl radical, an acyl group of 2 to 6 atoms of carbon, aroyl, alkoxycarbonyl of 2 to 6 carbon atoms, aryloxycarbonyl, alkylsulfonyl, arylsulfonyl, or an alkyloxalyl radical or alkoxyoxalyl of 3 to 6 carbon atoms;
- The fold:
a halogen atom, preferably chlorine, bromine or iodine, the sulfate group, an aryloxy or arylthio radical, optionally substituted, of preferably phenoxy, an alkoxy or dialkylamino radical, an R4O group when R4 is an acyl or arylsulfonyl group or alkylsulfonyl.
As a base, a strong base is used such as an alkali hydride or hydroxide or alkaline earth, an alcoholate or a tertiary amine. The reaction is practiced at a temperature between -30C and + 50 ~ C. The solvent is chosen from cyclic or non-cyclic ethers, dimethylforrnamide, dimethyl sulfoxide, acetonitrile or an aromatic solvent.
2s The preparation of the compound of formula Ia is described according to 2 modes of production.

We first describe a first mode of preparation of the compound of formula Ia, according to which the irnidazolinone cycle is constructed from ine ~ ediaries 21426 ~ 7 c ~, nlenal-l le ~ ruul) elllellt Ar2-X-Arl. This first mode of development of compounds according to the invention correspond to processes A, B, C, D described above after.

S Prep ~ r ~ tion of co ~ posed fornnlle Ia ~ l ~ nc Iaquelle n = 1 and Y = S:

oc ~ d ~ A:
The daring necks of formula (Ia) for which n = 1 and Y = S and W = S or O, in other words the compounds of formula II, are prepared according to one of the methods 0 described in European patent application EP 0 551 048, notal, ~ ne-.l by S-alkylation of the 2-thiohydantoins of formula (III), in which W l ~ pl ~ St.lle S
or 0, in ~ se-nce of a base and in a solvent, according to the reaction scheme next:

R ~ S, BaseR ~ ~ S - R2 Ar2 - X - Ar 1 ~ solvan ~ Ar2 - X - Ar l / ~ N ~ NH - R

(111) (He) in which, L, ~ n ~ sel.le a group chosen from a halogen atom, (of preferably chlorine, bromine, or iodine), or the alkyl sulfate group, alkylsulfonyloxy, or arylsulfonyloxy. As the base, a strong base is used such as an alkali or alkaline-earth alcoholate (preferably tert-butylate of potassium), an alkali or alkaline earth hydroxide, an alkali carbonate or alkaline earth or a tertiary amine. As the solvent an ether is used cyclic or non-cyclic, an alkyl ester, acetonitrile, an alcohol from 1 to 4 carbon atoms, a chlorinated solvent, an aromatic solvent. We use preferably solvent tetrahydrofuran (THF). The reaction is set in work at a l ~ lnl) elature between -5C and + 80C.

The following example illustrates this process.

`2 ~ 42647 F.xentple CFl: Preparation of (4-R, S) 4-methyl-2-methylthio-1-phenylarnino-

4- (4- (2-phenylethyl) pheny1) -2-imida ~ oline-5-thione (Compound No. 14).

s A 5 g (0.012 mol) of (4-R, S) 4-methyl-1-phenylamino ~ - (4- (2-phenylethyl) phenyl) irnidazolidine-2,5-dithione dissolved in 150 ml of THF
are added to 0C 1.36g (0.012 mol) of potassium tert-butoxide. After 15 minutes of stirring at this temperature, 1.5 ml (0.024 mol) of methyl iodide are added. Stirring is continued at 0C for 30 minutes, then after lo have let the ~, elature rise to room, the medium is hydrolyzed and extract with methylene chloride. After washing the organic extracts with a saturated sodium chloride solution, decantation, drying and evaporation of solvents, a brown oil is obtained. We crystallize this oil in a mixture of diisopropyl ether and pentane. After filtration, we l ~ upele 2.7 î5 g (0.006 mol) of (4-R, S) 4-methyl-2-methylthio-1-phenylamino4- (4- (2-phenylethyl) phenyl) -2-imidazoline-5-thione in the brown powder form melting at 118C with a yield of 49%.

The preparation of the compound of formula III is now described according to whether W
means S (compound of formula IIIa) or O (compound of formula IIIB).

Pre ~ r ~ tion of corr ~ posed form-lle m ~:

2s The dithiohydantoins of formula (IIIa) are oblel, ues from a compound of formula (IV), according to a process analogous to that described by T. Yamamoto and Coll. In J. Chem. Soc. Perkin Trans I (1990) Page 3003 to 3009, i.e.
depending on the reaction:

HH

><~~ + SR3 ~ H-- ~ H 2 R j><~ ~
Ar2 - X - Ar I ~ S Ar2 - X - Ar j ~~ NH - R3 S
(IV) (Illa) 2142 ~ 47 The following example illustrates the preparation of a compound of formula (II ~ a):

Fx ~ nlple C11:
Preparation of (4-R, S) 4-methyl- 1-phenylarnino4- (4- (2-phenylethyl) phenyl) imidazolidine-2,5-dithione, with structural formula:

NH - ~

A 22.6 g (0.066 mol) of (4-R, S) 4-methyl4- (4- (2-phenylethyl) phenyl) thiazolidine 2,5-dithione in lOOml of toluene, 6.7 ml (0.066 mol) of phenylhydrazine are added. The reaction medium is gradually heated to 60C then at reflux until gas evolution ceases. After the medium, hydrolysis is carried out, followed by extraction with ethyl acetate.
After decantation, drying of the organic phase and evaporation of the solvents, a black oil is obtained. After chromatography on silica color (Ethyl acetate / heptane 50/50), 11.2 g (0.027 mol) of (4-R, S) -4-methyl-1-phenylamino4- (4- (2-phenylethyl) phenyl) imidazolidine are recovered -2,5-dithione in the form of a brown powder melting at 171C with a yield of 41%.

The 2,5-thitholidine dithiones of formula (IV) are obtained from a isothiocyanate of formula (V), according to a process analogous to that described by T. Yamamoto et al. in J. Chem.Soc. Beijing Trans I (1990) Page 2459 to 2463, depending on the reaction:

- 214 ~ 6 ~ 7 ~ _.

I y + ~ S 2 Ar ~ --X - Ar I Ar ~ --X - Ar I ~ S

(V) ~ (IV) The following example illustrates the preparation of a compound of formula (IV):

FxPn ~ rle CI ~: Preparation of (4-R, S) 4-methyl4- (4- (2-phenylethyl) phenyl) thiazolidine 2,5-dithione, with structural formula:

~, ~ D ~ `

A 9.5 g (0.084 mol) of potassium tert-butoxide placed in 150 ml of THF to -70C, is added slowly a solution of 7ml (0.11 mol) of sulfide carbon and 20.4 g (0.076 mol) of 1- [4- (2-phenylethyl) phenyl] ethylisothiocyanate in 50 ml of THF. After 15 mimltes stirring at -70C the temperature is allowed to rise to ambient. After hydrolysis of the reaction medium with an aqueous solution of acetic acid, extraction with ethyl acetate, ~ léc ~ n ~ ion, drying of the organic extracts and evaporation of the solvents, 22.6 g (0.065 mol) of (4-R, S) 4-methyl4- are recovered (4- (2-phenylethyl) phenyl) thiazolidine-2,5-dithione in oil form with a 86% gross yield.

The isothiocyanate of formula (V) is prepared from an amine of formula (VI) in which the substituents have the same signifi ~ a ~ ion as in (V), according to one of the processes cited in Sulfur Reports (1989) Volume 8 (5) pages 327-375, either according to the reaction:

- 2 ~ 42 ~ 7 .

, s RI ~ 'IH 2base RIN
~ / + (~ SCI 2; ~ /
Ar ~ --X - Ar 1 / solvent Ar ~ --X - Ar 1 /
(Vl) (V) The following example illustrates the preparation of a compound of formula (V):

s Fx ~ CI ~: Preparation of 1- [4- (2-phenylethyl) phenyl] ethylisothiocyanate, developed formula:
N ~ C ~

To a suspension of 20 g (0.076 mol) of 1- (4- (2-phenylethyl) phenyl) ethylarnine in 200 ml of toluene at 0C is added 1 equivalent of sodium hydrogencarbonate in aqueous solution. After having reduced the temperature of the reaction medium to an arbiant temperature, 2 equivalents of sodium hydrogencarbonate in aqueous solution are added.
6.1 ml (0.076 mol) of thiophosgene in solution in 10 ml of toluene are then added slowly. At the end of the pouring, the stirring is continued for 15 miml ~? s. After decantation, the organic extracts are washed with water, dried then evaporated. 20.5 g (0.076 mol) of 1- [4- (2-phenylethyl) phenyl] ethylisothiocyanate in the form of an oil with a yield of 100%.

Prep ~ r ~ ioll du con ~ pos ~ de for ~ nule I ~ lb:

The 2-thiohydantoins of formula (IIIl), compounds of formula (III) in which W is the oxygen atom, are obtained according to the process described in the application of European patent EP 0 551 048, by a cyclization reaction of -` - 21 ~ 6 ~ 7 ._ 16 isothiocyanates of formula (VII) with hydrazines of formula R3-NH-NH2 according to the following reaction scheme:

><~ R3 - NH - hlH 2 RI> ~ N ~ 5 Ar2 - X - Arl ~ ORE Ar ~ --X-- ~ r ~ ~~ ~ NH - R3 o (Vll) (Illb) s in which RE the ~ l ~ saddles a C1-C3 alkyl radical.
Cyclization can be implemented according to 2 embodiments.
According to the first, the mixture of reagents is heated to a ~ elnl, elature included between 110C and 180C, in an aromatic solvent such as toluene, xylene, chlorobellzenes or nitrobenzene.
Io According to the second embodiment of the cyclization, we proceed in the presence of a strong base such as an alkaline or alkaline earth alcoholate, an alkaline or alkaline earth hydroxydeal, or a tertiary amine, at a tell ~ pe, ature cou.l, lise between -10 and ~ 80C and in a solvent chosen notanlmelll from an ether, a cyclic ether, alcohol, ester, DMF or DMSO.

The following example illustrates the preparation of a compound of formula (IIIB) F.xen ~ rle CI3 ': Preparation of (5-R, S) -5-methyl-3-phenylamino-5 - ((4-phenylthio) phenyl) -2-thiooxo-imidazolidin4-one with structural formula next:

[~ J ~ -N ~ ~

8.48 g (0.0258 mole) of (2-R, S) -2-isothiocyanato-2 - ((4-phenylthio) phenyl) -2s methyl propanoate are dissolved in 250 ml of tetrahydrofuran. 2.78 g (0.0258 mole) of phenylhydrazine are added dropwise. The middle 2 ~ 6 ~ 7 the reaction mixture is stirred for 30 minutes at t ~, nl) elal ~ lre ambient, coated in water and re-extract with ether. After drying over magnesium sulfate, the ether is evaporated to give 11.46 g of an oil which crystallizes. The crude reaction product is mixed with ether, filtered and recrystallized to give 3.36 g (0.0082 mole) of (5-s R, S) -5-methyl-3-phenylamino-5 - ((4-phenylthio) phenyl) -2-thiooxo-imidazolidin-4-one in the form of pink crystals melting at 158 C with a yield of 34%.

The a-isothiocyanato-esters of formula (VII) are prepared from the esters lo of α-amino acids of formula (VIII), in which the groups indicated have the same meaning that in formula (VII), according to one of the processes cited in SulfurReports (1989) Volume 8 (5) pages 327-375, either according to the reaction:

> ~ + CSCI 2; Rl> ~ = S
Ar2 - X - Arl ~ ORE Solvent Ar2 - X - Arl ~ (~) RE
O
lll) `(Vll) The following example illustrates the preparation of a compound of formula (VII):

F. ~ Pn ~ P1e C14: Preparation of (2-R, S) -2- (4-benzyloxyphenyl) -2-methyl isothiocyanatopropanoate To a stirred solution of 84.2 g (1.002 mol) of sodium hydrogen carbonate in 800 ml of water, 143 g (0.501 mol) of (R, S) - (4-benzyloxyphenyl) - are added -methyl methyl glycinate, then 800 ml of toluene; then we sink drop by drop drop at an arbiant temperature in 1.5 h while controlling gas evolution 40 2s ml (0.526 mol) of thiophosgene. After 2 hours of stirring at room temperature, decantation of the aqueous phase, washing with water, drying over sulphate magnesium and collcelltlation of the organic phase, 155.4 g (0.475 mol) are isolated of (2-R, S) -2- (4-benzyloxyphenyl) -2-isothiocyanatoplopdlloate under the form of a very thick oil with a yield of 95%.

21 ~ 647 By operating in an analogous manner, the following compounds of formula (VII) have been obtained:

R ~ ~ N = C = S

R ~ ~ oRE

R 'RE R1 Rdt Pf (C) 4-BnO Me Me 62% oil 4-Bn Me Me 50% oil 4-PhS Me Me 96% oil 4-PhSO Me Me 100% oil 4-PhSO2 Me Me 85% oil 3-BnO Me Me 80% oil The a-aminoesters of formula (VIII) are obtained by esterifying the a-amino acids of formula (IX), in which the groups indicated have the same lo sig.iil; cation only in formula (VIII), with an alcohol of formula REOH, in presence of thionyl chloride, process described in the literature by: M.
Brenner and W. Huber: Helv. (1953) Volume 36 Page 1109, as shown:

RI ~ H 2 SOCI 2 RI ~ NH 2 Ar2 - X - Arl / ~ OH REOHAr2 - X - Arl / ~ ORE
, OO
(IX) (VIII) The following example illustrates the preparation of a compound of formula (VIII):

F.xerr ~ ple CI ~: Preparation of (R, S) -2- (4-benzyloxyphenyl) -2-methyl-glycinate methyl ~ 2 & 4 '~

To a stirred suspension of 38.55 g (0.142 mol) of (R, S) -2- (4-benzyloxyphenyl) -2-methyl-glycine in 400ml of methanol maintained at -20C, 33.8 g (0.284 mol) of thionyl chloride are gradually added. Finally of addition, the solution obtained is allowed to rise to lel - arbbiante pelature, then the door at reflux for 16h. After concellllation, the residue is taken up in water and the solution obtained is basified with a concentrated aqueous solution sodium hydroxide at pH equal to 8. The precipitate is filtered, washed with water, wrung and dried under vacuum. After chromatography on 400g of silica gel in eluting with a heptane / ethyl acetate mixture 30/70 and concentration under the reduced pressure of the frictional fractions, 14.7 g (0.0515 mol) of (R, S) -2- (4-benzyloxyphenyl) -2-methyl methyl glycinate in the form of white powder with a melting point of 67C with a yield of 36%.

The table below gathers compounds of formula (~ IIII) synthesized.
R ~ \ / NH 2 R '~ ORE

R ~ R1 RE Rdtpf (C) or nD
4-BnO Me Me 36% 67 C
4-Bn Me Me 95% 112-116C
4-PhS Me Me 66% 1.6058 3-BnO Me Me 35% 50C

.

We now describe a variant preparation of certain α-amino esters of forrnule (VI ~), those for which X represents the group -S () n and which coll ~ syondent à la for ~ ule (VIIIb).
The a- ~ ni ~ loeJLels of forrnule (VIIIb) are obtained by oxidation of a-aminoesters of formula (VIIIa) according to methods described in Advanced Organic chemistry, J. March (1985) Page 1089 and 1090, 3rd Edition and according to 2s the diagram:

-` 21 ~ 2 ~

RI ~ NH 2 RI ~ NH 2 Ar ~ --S - Arl `h QRE Y ~ Ar ~ --S (O) n - Arl / ~ RE

(Vllla) (Vlllb) In this diagram n equals 1 or 2, RE has the meaning indicated for the definition of formula (VII).

The following examples illustrate the preparation of compounds of formula (VIIIb):

F.xelr ~ ple CI6: Preparation of (R, S) -2-amino 2 - ((4-phenylsulfinyl) phenyl) methyl propionate:

~ S ~

17.22 g (0.06 mole) methyl 2-amino 2 - ((4-phenylthio) phenyl) propionate are loaded into 350 ml of dichloromethane and cooled to 0C. 14.1 g (0.06 mole) of 73% metachloropell, ellzoic acid are added gradually in About 10 minutes. The reaction medium is stirred for ~ 2 hours at 0C. The precipitate is filtered and the organic phase is washed with normal sodium hydroxide and then with water and dried on magnesium sulfate. Evaporation leaves 15 g of an oil which is chromatographed on silica (eluent: ethyl acetate) to give 11.3 g (0.037 mol) of (R, S) -2-amino 2 - ((4-phenylsulfinyl) phenyl) propionate methyl in the form of a slightly yellow oil having an nD = 1.5979 at 25C
with a yield of 62%.

F.xelr ~ CI7: Preparation of (R, S) -2-amino 2 - ((4-phenylsulfonyl) phenyl) methyl propionate:

2 ~ 264 '~

~ NU2 ~ s ~
"~
oo 21.52 g (0.075) of (R, S) -2-amino 2 - ((4-phenylthio) phenyl) propionate methyl are loaded into 400 ml of methanol and cooled to 0C. 50.12 g (0.163 mole) 49.5% potassium persulfate dissolved in 400 ml of water are added dropwise over 1 hour at 0C. The reaction medium is agitated penda.ll 5 hours at room temperature. The residual oxidant is destroyed by 5 ml of a 30% solution of sodium hydrogen sulfite. The pH of the medium is brought to 8 el, vilon by adding 20 g of ca-l, sodium onate and the solid is filtered. After stirring the solid in 500 ml of dichloromethane, then filtration o of the residual solid, the filtrate is dried and the solvent evaporated to give 16.9 g (0.529 mol) of (R, S) -2-amino 2 - ((4-phenylsulfonyl) phenyl) propionate methyl in the form of white crystals melting at 124 C with a yield of 70 ~.

The α-amino acids of formula (IX) are obtained by hydrolysis of hydantoins corresponding (X) in acidic or basic medium according to a process analogous to that described in the Dutch patent Nl ~ 69 00349 or in J. Org. Chem.
(1985) Volume 50 Page 1876 to 1878, or according to the diagram:

R j> ~ n ~ 3 base R; ~ <~ H 2 Ar2 - X - Ar j ~ NH Ar2 - X - Ar fh ~ H

(x) (lx) The following example illustrates the preparation of compounds of formula (IX).

5 Fx ~ rr ~ ple CI8: Preparation of (4-R, S) -2- (4-benzyloxyphenyl) -2-methyl-wisteria `214 ~ 2 ~ 47 To a stirred solution of 40g (1 mol) of sodium hydroxide in 100 ml of water, 17.2 g (0.0506 mol) of (5-R, S) -5- (4-benzyloxyphenyl) -5-methyl- are added hydantoin and the suspension obtained is refluxed for 24 hours. After s cooled ~ ellt, the reaction medium is neutralized with an aqueous solution concentrated hydrochloric acid then the suspension is diluted with 100 ml of water. The preci ~ is filtered, washed with water and then with acetone, drained and dried under vacuum.
16.2 g at 87 mol% are thus isolated by NMR of (R, S) -2- (4-benzyloxyphenyl) -2-methyl-glycine as a white powder with a melting point 0 SUpl ~ l ielll at 300C.

The table below brings together the α-amino acids of formula (IX) synthesized:

Rl ~ NH 2 is R ~

R 'R1 Rdt pfc or nD
4- (3-Pyridyloxy) Me 96%> 300C
4-BnO Me 42%> 300C
4-Bn Me 100 ~> 300C
4-PhS Me 100%> 300C
3-BnO Me 100% 270C
3-PhS Me 100 ~> 300C

The hydantoins of formula (X) are obtained by Bucherer-Berg reaction on the corresponding acetophenones, process described in the literature: Chem.
Rev. (1950) Volume 46 page 422425 or Chem. Pharrn. Bull. (1973) Volume 21 pages 685 to 691. Said acetophenones are easily accessible to humans of career.

2 ~ 426 ~ 7 ed ~ B:

According to a preferred embodiment, the compounds according to the invention of formula s (II), in which W l ~ plésenle an oxygen, au ~ ent says the compounds of formula (IIa), are prepared by reacting successively the compound of formula (VII) with a hydrazine of formula R3-NH-NH2, then with a base of formula B-M +, and finally with an alkylating agent of formula R2L, in which L and R2 are defined as above with the restriction that R2 is lo different from the hydrogen atom.
The base is chosen by an alkali or alkaline earth alcoholate, a hydroxide alkaline or alkaline earth, or a tertiary amine. The reaction is carried out at a temperature between -10 and + 80C and in a chosen solvent nolall ~ llent including a cyclic or non-cyclic ether, an alcohol, an ester, DMF, DMSO, acetonitrile or among an aromatic. The reaction scheme is the next:

><+ R 3-- ~ H - ~ H 2 B M + ~ RI ~ N ~ M +
At ~ --X - Ar i ~ OR E Ar ~ --X - Ar i ~~ ~ NH --R 3 , ~, _ (Vll ~
R 2L ~ R ~~ S - R ~

Ar ~ --X - Ar i ~~ ~ NH --R3 (lla ~

The following example illustrates the preparation of formula compounds (IIa).
Fx ~ n ~ CF ~: Preparation of (4-R, S) -4-methyl-2-methylthio-4- (4-phenylthiophenyl) - I -phenyiamino-2-imidazoline-5-one (compound N 25):

~ a stirred solution of 5 g (0.015 mol) of (2-R, S) -2- (4-phenylthiophenyl) -2-2s methyl isothiocyanatopropanoate in 120 ml of anhydrous tetrahydrofuran under nitrogen blanket 1.62 g (0.015 mol) of phenylhydrazine is added; we let react for 1 h at room temperature then the reaction medium is cooled to 21Q2 ~ 47 0C. 1.68 g (0.015 mol) of potassium terliobutylate are added, the reaction is allowed to proceed 0.25 h then 2.13 g (0.015 mol) of methyl iodide are added. Let the telnpél ~ lure rise to the ambient and stir for 3 h. We pour the reaction medium in 100 ml of water and then the product is extracted with acé ~ ate of ethyl. After washing at 1 ' water, drying over magnesium sulphate and concentration of the organic phase is recovered 7.4 g of a honey which is dissolved in 30 ml of diisopropyl ether. The product precipitates at 5C; after filtration and drying under reduced pressure, one obtains 4.8 g (76%) of (4-R, S) -4-methyl-2-methylthio-4- (4-phenylthiophenyl) -1-phenylamino-2-imidæoline-5-one (compound N 25) in the form of beige crystals melting at 1 3 ~ C.

Plé ~ tion of corrq) daring for ~ nt11e I ~ nc l ~ which n = 1 and Y = O:

The preparation of the compounds of formula (Ia) for which n = 1 and Y = O and W = O, aulrt: l ~ lellt the compounds of formula (XI).

Method C:
These compounds are obtained by reacting in a solvent the 2-alkylthio-2-2 ~ imidazoline-5-ones of formula (II) with an alcohol R20H in ~ l ~ sence of a base strong, according to the diagram:

> ~ q / + R20 ~ 1 ~ R ~ lq ~ O - R2 A ~ '~ --X - Arl h-- ~ NH - R3 solvent Ar ~ --X - Arl ~~ N ~ NH - R3 WW
(He) '(Xl) 2s in which R'2 leplesellle an allcyle group co ~ renant of 1 to 3 atoms of carbon.
As a strong base, an alkaline alcoholate R ~ O-M +, a hydroxide can be used.
alkaline, an alkaline earth hydroxide or a strong organic base. The reaction is preferably carried out in alcohol R20H, solvent, and using the corresponding sodium alcoholate R2O ~ Na + as a base. The reaction is `21426 17 practiced at a lem ~ élatllre between 20 and 80C. According to a variant of process, the reaction is carried out in the presence of an oxidant. As an oxidant can use notan ~ l, ellt sodium or potassium periodate.

s The following example illustrates the preparation of the compounds of formula (XI):

FY ~ n ~ ple CF3: Preparation of (4-R, S) 4- (4-benzyloxyphenyl) -2-methoxy4-methyl-1-phenylamino-2-imidazoline-5-one (compound N 9):

To a solution of 0.5 g (0.0093 mole) of sodium methylate in 50 ml of anhydrous methanol under an inert atmosphere, 2.6 g (0.0062 mol) of (4-R, S) 4- (4-benzyloxyphenyl) -4-methyl-2-methylthio- 1-phenylamino-2-imidazoline-5-one and 1.3 g of sodium periodate. We heat at reflux for 6 hours. After the reaction medium has cooled, it is neutralized with acetic acid, pour it into 100 ml of water and extract it with dichlolomethane. The organic phase is washed with water, dried over sulphate magnesium then concentrated under reduced pressure. The raw airlsi product obtained is purified by chromatography on silica (eluent: heptane / ethyl acetate 50 / 50). The purified product is crystallized from diisopropyl ether. After pre-filtration and drying under reduced pressure, 0.8g (0.002mol) of (4-R, S) 4- (4-benzyloxyphenyl) -2-methoxy4-methyl-1-phenyla ~ nino-2-imidazoline-5-one (compound N 9) in the form of white crystals having a melting point of 127C with a yield of 32%.

2s Preq ~ ioîl coî ~ posed to form la rlan ~ la-luelle n = 0:

~ oc ~ th D:

The preparation of the compounds of formula (Ia) for which n = 0 and W = O, in other words the collposites of formula (XII):

- 2 ~ 42647 R ~ q ~ R2 Ar2 - X - Ar I ~~ ~ NH - R3 (Xll ~
These compounds are prepared according to the process described in the application.
WO 94/01410, that is to say by reacting a hydrazine of formula R3-NH-NH2 on an azalactone of formula (XIII), according to the scheme following reaction:

R ~ q ~ R2 R ~> ~ Nq ~ R2 Ar ~ --X - Ar I h-- ~ CH3COOH Ar2 - X - Ar I ~ N ~ NH-- ~.

(Xlll) (Xll) The reaction is carried out by heating the mixture of reactants in acetic acid at reflux, optionally in plesence of sodium acetate as catalyst.

The following example illustrates the preparation of compounds of formula (XII).

Fx ~ n ~ C18 ': Preparation of (5-R, S) -2-ethyl-5-methyl-3-phenylamino-5 - ((4-phenylthio) phenyl) -imidazolidin-4-one: of structural formula:

CH3 N ~ CH2CH3 [~ SJ ~ N ~

4 g (0.013 mole) of (4-R, S) -2-ethyl-4-methyl 4 - ((4-phenylthio) phenyl) -3-oxazolin-5-one are added to 100 ml of acetic acid. 1.4 g (0.013 mole) of phenylhydrazine are poured dropwise into the reaction medium. The reaction medium is heated at reflux for 2 hours then acetic acid is removed under vacuum. The residue is mixed with water, neutralized, then re-extracted with dicholorolnétl, donkey. After drying over mag sulfate ~ léçiu.l., The evaporation of - 2 ~ 6 ~ ~;

solvent leaves 4.09 g of an oil which is chromatographed on silica (eluent:
ethyl acetate / heptane 4/1) to sleep 3.41 g (0.0085 mole) of (5-R, S) -2-ethyl-5-methyl-3 ^ phenylamino-5 - ((4-phenylthio ) phenyl) -imidazolidin4-one under form of an oil which is crystallized from diisopropyl ether as s beige crystals melting at 90 C with a yield of 66%.

The azalactones of formula (XIII) are obtained by reacting the a-amino acids of formula (IX) with a carboxylic acid anhydride, according to a process described in the literature: R. Cotton et al., Int. J. Peptide Protein lo Res. (1986) Volume 28 Page 230 to 244 and according to the diagram:

> ~ R2COOcoR 2 RI ~ N ~ R2 Ar ~ --X - Ar I ~ H Ar ~ --X - Ar t /) ~

(IX) `(Xlll) The following example illustrates this process for the preparation of the compounds of formula (XIII).

F.xelnple CT9: Preparation of (4-R, S) -2-ethyl4-methyl ~ - ((4-phenylthio) phenyl) -3-oxazolin-5-one of structural formula:

NJ
~ S ~ O '~

14.2 g (0.052 mole) (2-R, S) -2-amino-2 - ((4-phenylthio) phenyl) acid propionics are put in ~ u ~ l) ellsion in 200 ml of propionic anhydride. The medium is heated at reflux for 1 hour then the propionic anhydride is 2s removed under pump vacuum by azeotropy by adding heptane. The residue (16 g) is dissolved hot in 100 mt of ethanol. A white solid crystallizes (3.0 g) which is filtered and discarded. The juices are reconconcles to give 12.3 g of an oil brown which is chromatographed on silica (eluent: ethyl acetate / heptane 4 /

2 ~ 4 7 1) to give 4.76 g (0.0153 mole) of (4-R, S) -2-ethyl4-methyl ~ - ((4-phenylthio) phenyl) -3-oxazolin-5-one in the form of oil (NMR 250 MHz -CHCl3 - in ppm: 1.3 (t, 3H); 1.75 (s, 3H); 2.58 (q, 2H); 7.2 to 7.6 (m, 9H)) with a yield of 29%.

We now describe a second embodiment of the compound of formula Ia according to the invention, according to which an Ar2-X group is introduced on a imidazolinone of formula (XIV):

R 1 N ~ (Y) n - R 2 Arl> ~ `NH - R3 W

(XIV) This second embodiment corresponds to the methods E, F, G, H, I, J, K, L, M which are defined above.

1S Proc ~ d ~ E:
The preparation of the compounds of general formula (Ia) is first described:
Rl N ~ (~ n - R2 Ar2 - X-Ar ~> ~ `NH - R3 W
(the) in which X has the same meaning as a group X ', which is defined above below darls the description of process E.
The compounds of general formula (Ia) are obtained by condensation of a organometallic derivative of an imidazolinone of formula (XV) with a radical el. llophile Ar2-X '+ according to the reaction scheme:

2 ~ 4 ~ 6 ~ 7 _ RI ~ N ~ (Y) r ~ 2 1) Ar2-X '+ Rl Nq ~ (~ --R2 M ~ Arl `h - N` N - R3 2) H20 Ar2 - X - Ar ~> ~ NH - R3 WMW
(XV) (the) in which Ml the ~ l ~ selllè a metal chosen from lithium, sodium, magnesium, zinc, titanium, tin, copper, boron or silicon and is preferably lithium, and in which X 'is such that Ar2 ^ X' is a radical electrophile generated by a compound chosen no ~ nmenl from:
a halide or an aralkyl sulphate of formula Ar2-RI2 ^ L
in which:
- Rl2 ~ eplesellle an aliphatic chain of 1 to 6 atoms of o carbon, linear or branched, saturated or unsaturated é ~ additionally substituted by a halogen or a group alkoxy or an oxo radical; and - L has the same meaning as precedell.lllelll;
- a carbonyl compound of formula:
Ar2 - (R 12) P - CR 13 o in which:
-p = Where l;
^ Rl2 has the same meaning as above; and - Rl3 leplesellte the hydrogen atom, a Cl-C6 group alkyl, halogen, alkoxy, aryloxy, or dialkylamino;
^ a chloroforrnate of formula:
Ar2- (R 12) P - O - ICl - Cl in which p and R12 have the same meanings as ci ^
2s above;
^ an isocyanate or an isothiocyanate of formula:
Ar2- (R 12 ~ P - N = C ~ (?

- 2142 ~ 17 in which p and Rl2 have the same meanings as above above, and Q tepl ~ se ~ te the oxygen or sulfur atom;
- a sulfonyl halide of formula:
"
Ar2 - (R 12) P-- Hal o s in which Rl2 and p have the same meanings as previous., llne-ll and Hal lel ~ lesellle a halogen atom, preferably the chlorine atom;
-an epoxide of formula:

Rlo Ar2 ~ / R l0 O

When, according to a preferred variant of the invention, the letter Ml of the formula (XV) lepl ~ senle lithium, the compounds of formula (XV) correspondallls, that is, the organolithians of formula (XVII), are obtained at from halogenated derivatives (XVI), in which Hal lepli ~ sellle an atom halogen, preferably chlorine or bromine, by halogen metal exchange (Hal) comrne described by RG JONES and H. GILMAN, Organic Réactions (19), volume 6, page 339. The reaction is as follows:

R Nq ~ (y) n - R2 nButyl lithium RIN ~ (Y) n - R2 Ha ~ --A ~ R.3 ~ Li - Ar l> ~ `N - R3 (XVI) (XVII) When the letter Ml of the formula (XV) does not fill in, it does not contain lithium, ol ~ olll ~ lalliques of formula (XV) corresponding can be obtained at to grow organolithians (XVII) by transmetallation reaction as described in Advanced organic chemistry, J. March, (1985), p. 557, 3rd Editing.

2 ~ 2647 The following example illustrates the preparation of a compound of formula (Ia).

F. ~ en ~ ple CF4: Preparation of (4-R, S) -4- [4 - ((4-s chlorophenyl) hydroxymethyl) phenyl] -4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one (compound N 30):

1 g (0.0025 mol) of (4-R, S) -4- (4-bromophenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazolin-5-one is dissolved under an inert atmosphere in 20 ml o of anhydrous THF then the reaction medium is cooled to -70C. At this l ~ ln ~ elature are added 2 equivalents of n-butyllithium (3.2 ml of solution 1.6 M hex). After 15 minutes of stirring at -70C 0.36g (0.0025 mol) of 4-chlorobenzaldehyde is added in solution in 3 ml of THF. After 30 minutes of reaction the reaction medium is hydrolyzed at -70C with a saturated solution of Arnmonium chloride. After extraction with ethyl acetate, washing the organic extracts with a saturated sodium chloride solution, drying, evaporation of the solvents, and chromatography on a silica column of the product crude (ethyl acetate / Heptane: 50/50), 0.95 g (0.002 mol) of a white solid which is (4-R, S) 4- [4 - ((4-chlorophenyl) hydro ~ yl ~ yl) phenyl] 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one, having a 94C fusion with 82% yield.

The 2-irnidazoline-5-ones of formula (XVI) are obtained by one of the methods described in European patent application EP 0 551048 published on July 14 1993, in the case where Y = S and n = 1; according to a process analogous to process C
described previously ~ in the case where n equals 1 and Y signifies O; either according to a process analogous to the method D described above when n is 0.

Method F:
The preparation of the compounds of general formula (Ib) is now described:

21 ~ 264 ~

._ 32 Rl N ~ {~ n - R2 Ar2 - (R'l2) p - Z - Arl> ~ N ~
WH
(Ib) in which p and Z have the same meanings as above ~ nelll, and R '12 lep. ~ saddles an aliphatic chain of l to 6 carbon atoms, linear or Sarnified, saturated or unsaturated.
These coll.lposés are obtained according to known methods by reacting a imidazolinone of formula (XVI) with a nucleophile of formula (XVIII) according to a plocécé similar to that cited in Comprehensive heterocyclic chemistry, A.
R. Katritzky, Volume 2, Part 2A, Page 359, or according to the diagram:

Rl Nq ~ {Y) n - R2 Ar ~ - (R 12 ~ P - i ~ H Rl N ~) n - R2 Hal - ArI> ~ N ~ _R3 Ar ~ - (R '12) P - Z - Arl> ~ N ~ N - R
HW
(XVI) (Ib) The reaction is carried out under the conditions usually employed in aromatic substitution reactions.

The following example illustrates the preparation of compounds of formula (Ib).

F.xernple CF5: Preparation of (4-R, S) 4- [6- (4-fluorophenylthio) -5-nillopylidine-2-yl] -4-methyl-2-methylthio-1-phenylamino-2-irnidazoline-5-one (Compound N 64):

To 1.00 g (2.5 mmol) of 4- (6-chloro-5-nitro-pyridin-2-yl) 4-methyl-2-methylthio-l-phenylamino-2-irnidazoline-5-one in solution in 50 ml of acetone under argon 2s are added to tenlpel ~ ambient ture lg of K2CO3 then 0.27 ml (2.5 mmol) of 4-fluorothiophenot. After 2 hours of reaction at room temperature, the medium is diluted with water; the product is extracted with ethyl acetate; extracts 21 ~ 26 ~

_ ~ 33 are dried over anhydrous magnesium sulfate and then conce ~ s under pressure scaled down. The product after chromatographic purification on silica (Eluent:
ethyl acetate / Heptane 20/80) is crystallized from diisoplupyl ether.
On ~ ul) èl ~ after filtration and drying 0.8g (1.66 mmol) of (4-R, S) 4- [6- (4-s fluol oyhellylthio) -5-nitropyridine-2-yl] 4-methyl-2-methylthio- 1 -phenylamino-2-imidazoline-5-one (Compound N 64) in the form of crystals having a point of merger of 171C with a yield of 66%.

Method G:

The preparation of the compounds of formula (Ic) is now described:
Rl N ~ (Y) n - R2 Ar2 - X - O ~ --N `N - R

in which X 'has the same meaning as before.
The compounds of formula (Ic) are obtained by reaction of a 4-(hydroxyphenyl) -2-imidazoline-5-one, of formula (XIX), with a radical electlol) hil Ar2-X '+ according to the reaction scheme:

HO ~ q ~ Ar ~ --X '~ qN ~ (-Y) n ~
WI Ar2 - X '- ~ --R3 The reaction is carried out in basic medium under the conditions usually used for condensation between phenols and different radicals electrophiles (methods known per se in the literature). As a basis we can use, notanlll.ell ~, carbonates and alkali or alkaline earth hydroxides, organic bases. The reaction is carried out at a te, llpéla ~ e col "~ read between + 20C and + 150C. It is carried out in solvents such as alcohols, 21 ~ 26 ~ 7 .

ketones, acetonitrile, aliphatic esters, ethers, cyclic ethers, aromatic solvents, chlorinated solvents, dimethylformamide, dimethyl sulfoxide, N-methylpyrolidone.

The following example illustrates the preparation of compounds of formula (Ic).

F. ~ t ~ ple CF6: Preparation of (4-R, S) 4-methyl-4- (4- (3-methylbenzyloxy) phenyl) -2-methylthio-1-phenylamino-2-imidazoline-5-one (compound N 22):

To a stirred solution of 2g (0.0061 mol) of (4-R, S) 4- (4-hydroxyphellyl) -4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one in 50 ml of ethanol, 0.92 g (0.0067 mol) of potassium carbonate is added 0.94 g (0.0067 mol) of 3-methylbenzyl chloride and 0.1g (0.00061 mol) of potassium iodide. We brings the reaction medium to reflux for 8 hours. We pour it in 150 ml of water. The plecipitate formed is washed with an aqueous 1N hydroxide solution.
sodium, then with water until neutral, drained, washed with diisoplopyl ether then dried under reduced pressure. 1.94 g (0.0045 mol) of (4-R, S) -4-methyl4- (4- (3-methylbenzyloxy) phenyl) -2-methylthio-1-phenylami are thus obtained; lo-2-imidazoline-5-one (compound N 22) in the form of white crystals having a point of 151C with a yield of 75 ~.

The hydroxylated compounds of formulas (XIX) are obtained from corresponding benzylated compounds (Id), removing the benzyl group by means of a so-called debenzylation reaction. Debenzylation is carried out according to methods usually used, either by a hydracid or by hydrogenation catalytic, and known in the literature: G. Buchi and SM Weinreb, J. Am.
Chem. Soc. (1971) Vo1ume 93 Page 746 or O. Th. Schmidt and H. Schmadel, Annalen (1961) Volume 649 Page 149. The reaction scheme is as follows:

2 ~ 42 ~ 17 q '' HX, CH ~ COOH Rl Nq ~ (Y) n - R2 ~ _N ~ N _Ru H 2 catalyst ~ _N `Nl - R3 ~, (Id) (XIX) The following example illustrates this process for the preparation of the compounds of formula (XIX).

Fx ~ rr ~ ple CI10: Preparation of (4-R, S) 4- (4-hydroxyphenyl) 4-methyl-2-n ~ yll} lio-1-phenylamino-2-ilnidazoline-5-one, of structural formula:

\ /

~ N ~ ~ o ~
To a stirred suspension of 31.2 g (0.075 mol) of (4-R, S) 4- (4-benzy-0 1o ~ ylJhéll ~ 1) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one in 370 ml of acetic acid is added 92 ml of concentrated hydrochloric acid (d = 1.18) and it is heated to 75C for 2h. After cooling the reaction medium to Tell room temperature, we pour it in 500 ml of ice water and then neutralizes the medium with a concentrated aqueous solution of hydroxide sodiuin. The fold: ci ~ é formed is stirred for 1 h at 5C then filtered, washed with water, wrung out and dried under reduced pressure. 22g (0.067 mol) of (4-R, S) -4- (4-hydroxyphenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one under form of white crystals having a melting point of 206C with a yield 90%.
The table below gathers the imidazolinones of formula (XIX) synthesized:

`2142 ~ 7 ~ HN ~

Position OH Yield (%) pF (C) The 4- (Benzyloxyphenyl) -2-imidazoline-5-ones (Id) are obtained according to one of s processes described above ~ lle ~ océd ~ H:

lo We now describe the preparation of the compounds of formula (Ie):
Rl Nq ~) n - R2 Ar2 - (R 12) P - Z ~ a ~ N`N - R

in} watercolors p and R '12 have the same meaning as before ~ enl and Z' replicates the oxygen, sulfur, or N-RI4 group, in which R14 the ~ senle the hydrogen atom or a C1-C6 alkyl group.

These compounds are obtained by reacting derivatives of 4- (carboxyphenyl) -2-imidæoline-5-one of formula (XX), with a chlorinating agent such as thionyl chloride, oxalyl chloride or phosgene, optionally in 2 ~ p, ~ sence of a catalyst such as dimethylformamide and in an inert solvent;
then with a nucleophilic compound of formula: Ar2- (R '12) p-Z'H (XVIII), in pl ~ sence of a base such as an alkali or alkaline earth carbonate or a organic base, according to the diagram:

`2 ~ 426 ~ 7 _. 37 RI ~ lq ~) n - R2 RI Nq ~ (Y) n - R2 H ~ l -C {~~ N `Nl - R3 Cl C

(XX) (XXI) Ar2 - (R 12) P - Z ~ HRI Nq ~ (Y) n - R2 Ar2 - R '12 - Z'-C ~~ 1-1 (the) The following example illustrates this process for the preparation of the compounds of formula (Ie).

Fxerr ~ ple CF7: Preparation of (4-R, S) 4- (4- (4-chlorophenylaminocarbonyl) phenyl) 4-methyl-2-methylthio-1-phenylamino-2-lo imidazoline-5-one (compound N 45):

lg (0.0028 mol) of (4-R, S) -4- (4-carboxyphenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one is dissolved in 20 ml of 1,2-dichloro-ethane at te.npé. ~ ambient ture. To this l ~ p ~. ~ Ture are added 0.5 ml (0.0056 mol) of oxalyl chloride then a drop of dimethylformamide. At the end of evolution of gas, the solvent is evaporated and the acid chloride is taken up in 20 ml of anhydrous THF. 0.4 ml are then added at room temperature.
(0.0028 mol) of triethylamine then 0.71 g (0.0056 mol) of 4-chloroaniline.
After 1 hour of stirring, the medium is hydrolyzed. After acetate extraction ethyl, washing the organic phases with saturated chloride solution sodium, drying, evaporation of solvents lg of brown oil is l ~; I; U ~. After crystallization from diisopropyl ether, filtration and drying, 0.85 g is isolated (0.0018 mol) of (4-R, S) -4- (4- (4-chlorophenylaminocarbonyl) phenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one as a beige solid having a melting point of 210C with a yield of 65 ~.

~ 2 ~ 7 The 4- (carboxyphenyl) -2-ilnidazoline-5-ones of formula (XX) are plel, al; s in reacting an organolithian of formula (XVII) with carbon dioxide according to a process analogous to that cited in Advanced organic chemistry, 1. March, (1985) Page 826 3rd Edition, in other words according to the reaction:

R Nq ~ Y) n - R2 RIN ~) n - R2 Li - Ar 1) ~ `N - R3 H 3 HO 2 (~ ~ N` Nl - R3 (XVII) (XX ~

The reaction is carried out by bubbling carbon dioxide into the medium l ~ reaction containing the organolithium.

The following example illustrates this process for the preparation of the compounds of formula (XX).

F ~ x ~ ntple CIl 1: Preparation of (4- ~, S) -4- (4-carboxyphenyl) 4-methyl-2-methylthio-1-phenylamino 2-irnidazolin-5-one, of structural formula:

HO ~ ~

lg (0.0025 mol) of (4-R, S) 4- (4-blomophellyl) 4-methyl-2-metllylthio-1-phenylamino 2-imidazolin-5-one is dissolved under an inert atmosphere in 20 ml anhydrous tetrahydrofuran. The reaction medium is cooled to -70C. To this ~, elature are added 2 equivalents of n-butyllithium (3.2 ml of solution hexaniquel, 6 M). After 15 minutes of stirring at -70C, the dioxide is bubbled dry carbon. After 30 min, the reaction medium is hydrolyzed at -70 C.
After extraction with ethyl acetate and then washing the organic phase with a saturated potassium carbonate solution, the aqueous phases are combined and then acidified. After extraction with ethyl acetate, drying, evaporation of the "21'1 ~ 6 ~ 7 solvents, lecu ~ 0.5 g (0.0014 mol) of (4-R, S) 4- (4-carboxyphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazolin-5-one in powder form white melting at 183C with a yield of 56%.

Method I:

We now describe the plepalalion of compounds of general formula (If):
Rl N ~) n - R2 Ar2 - (R '12) P-- ~ -CHR `[~ N ~ Nl - R3 in which R '12, p and Z' have the same meaning as "" llelll, and Rlel "ese" ~ e a hydrogen atom, an alkyl, haloalkyl, alkoxyalkyl or alkylidene, each of these coll alkyl radicals, the ellalll of 1 to 6 atoms c & ll ~ one. R consel ~ e this same definition in the rest of the descliplion.
These necks, lyosed, are obtained by reaction of a nucleophilic compound of formula Ar2- (R'12) p-Z'H (XVIII) with a 4- (chloromethylphenyl) -2-imidazoline-5-one of structure (XXIII).
The reaction is carried out in plesellce of a base under the conditions usually practiced for condensation between alcohols and dirr ~ len ~ electrophilic and known in the literature: Advanced organic chemistry, J. March, (1985) Page 342 3rd Edition, at ~, enlelll says according to the reaction scheme:

~ $ f (Y) n - R2 Ar2 - (R '1-2) p - ZH ~ f (Y) n - R2 XCHR ~ W I - R3 Ar2 - (R '12) P - Z - CHR ~ --1 ~ 3 (XXIII) (If) 2s -21 ~ 2647 .

As a base, it is possible to use carbonates and alkali hydroxides or alkaline earth or organic bases. The reaction is practiced at a l ~ n.pélature between 2 ~ C and 150C. The reaction is carried out within solvents such as alcohols, acetonitrile, aliphatic esters, ethers, cyclic ethers, aromatic solvents, chlorinated solvents, ketones, dirnethylformamide, dimethylsulfoxide, N-methylpyrolidone.

The following example illustrates this process for the preparation of the compounds of forrnule (If).

F.xelT ~ CF8: Preparation of (4-R, S) 4- (4 - ((2,4-difluorophenoxy) methyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one (compound N 47) 0.3 g (0.0083 mol) of (4-R, S) -4- (4-chloromethyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one is mixed in DMF with 0.11 g (0.0083 mol) of 2,4-difluorophenol, 0.12 g (0.0083 mol) of carbonate potassium and 0.14 g (0.0083 mol) potassium iodide. The mixture reaction is brought to 80C for 2h. After hydrolysis with water, extraction at ethyl acetate, washing the organic extracts with a saturated solution of lithium chloride, drying and evaporation of the solvents, the honey obtained is crystallized from diisopropyl ether and then filtered. This is licked 0.250 g (0.0055 mol) of (4-R, S) 4- (4 - ((2,4-difluorophenoxy) methyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in the form of a precipitate beige-fondant at 152C with a yield of 66%.

The 4- (chloromethylphenyl) -2-imidazoline-5-one of structure (XXIII) are obtained by halogenation of 4- (hydroxymethylphenyl) -2-irnidazoline-5-one of structure (XXII). The halogenation is carried out according to methods usually used for this type of reaction using hydracid or acid halide inorganic such as SOC12, PCls, PC13, POCl3 as cited in Advanced organic chemistry, J. March, (1985), Page 382, 3 rd Edition and according to reaction scheme:

2f 426 ~ 7 _ 41 q ~ {POX 3 or PX 3 or PX 5 Rt Nq ~ () 2 HOCHR {~ N ~ NR ouHXOusOcl 2 ~ N ~ I_R3 (XXII) (XXIII) The following example illustrates this process for the preparation of the compounds of structure (XXIII):

Fl ~ rrq ~ CI12: Preparation of (4-R, S) 4- (4-chlolonlelhylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one, of structural formula:

\ / q ~

Cl ~ ~ 0 lo Has a solution of 0.9 g (0.0026 mole) of (4-R, S) 4- (4-hydroxymethylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in 10 ml of toluene, are added to lel.lp ~ ambient lature 0.22 ml (0.0026 mole) of pyridine then 0.2 ml (0.0026 mole) of thionyl chloride dissolved in 1 ml of toluene. The reaction mixture is brought to 60C for 3 h then cooled and hydrolyzed.
After extraction with ethyl acetate, wash the organic extracts with a saturated sodium chloride solution, drying and evaporation of the solvents, a yellow honey is obtained. After chromatography on a silica column (Acetate ethyl / Heptane: 50/50), it is 0.36 g (0.001 mole) of (4-R, S) 4- (4-chloromethylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in the form of a yellow powder ~ waving at 130C with a yield of 38%.

The (hydroxymethyl) phenyl-2-imidazoline-5-ones of frrnules (XXII) are obtained by reduction of carbonyl compounds (XXIV) gluesl) olldants. This reduction can be carried out according to methods usually used for this type of reaction, described in the literature: Advanced organic chemistry, J.
March, (1985) Pages 1093-6 3rd Edition and according to the diagram:

214 ~ 647 ._ R-Cff ~} H ~ CHR ~ ¦
`` (XXlV) (XXII) I, the following example illustrates this process for the preparation of the compounds of S structure (~ XII):

Fx ~ n ~ ple CI13: Preparation of (4-R, S) 4- (4-hydro ~ yn ~ ylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one, of structural formula:

HO ~ --N ~ NH ~
To a solution of 9 g (0.0026 mole) of (4-R, S) 4- (4-formylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in 100 rnl of ethan ~ l absolute at 0C are added 1.02 g (0.0026 mole) of NaBH4. After 4 hours of agitation at an.bia..le temperature, the medium is hydrolyzed and then extracted with ethyl acetate.
The organic extracts are washed with a saturated solution of chloride of sodium, dried, evaporated and chromatographed on a silica column (Acetate ethyl / heptane: 50/50). on ~ 0.9 g (0.00026 mole) of (4-R, S) 4- (4-hydro ~ ymélllylphenyl) 4-methyl-2-methylthio-l-phenylamino 2-imidazoline-5-one in the form of a brown powder melting at 146C, with a yield of 10 ~.
The table below gathers the imidazolinones of formula (~ fXII) synthesized;

N

21,426 ~

OH position X Yield (%) pF (C) The carbonyl compounds of formula (XXIV) are prepared by reaction of a s organolithian of formula (XVII) with a carbonylated electrophilic compound such as described by J. EVANS, J. Chem. Soc, (1956), page 4691 and according to the diagram reactionary:

R ~ Nq ~) n - R2 R -C-- ~ RIN ~ (Y) n - R2 Ar ~ N`N - E ~ 3 2) H 20 RC ~ N`NI - R3 (XVII) `(XXlv The following example illustrates this process for the preparation of the compounds of structure (XX ~ V):

Fx.on ~ CI14: Preparation of (4-R, S) ~ - (4-formylphenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one, of structural formula:

\ /

o N ~ NH
1 g (0.0025 mole) of 4- (4-bromophenyl) 4-methyl-2-methylthio-1-phenylamino-2-irnidazoline-5-one is dissolved under an inert atmosphere in 20 ml of THF
anhydrous and then brought to -70C. At this temperature are added 2 equivalents of `- 2 ~ 2647 nBuli (3.2 ml; 1.6M). ~ nearly 15 minutes of stirring at -70C, 0.2 ml (0.0025 mole) of dimethylformamide is added in solution in 1 ml of THF. After 30 minutes, the medium is hydrolyzed at -70C with a saturated chloride solution ammonium. After extraction with ethyl acetate, washing of the phases S organic with saturated sodium chloride solution, drying, evaporation of the solvents, and chromatography on a silica column of the product crude (ethyl acetate / heptane: 50/50) 0.55 g of light yellow oil yr ~ ciyitant in isopropyl ether is obtained. 0.35 g (0.001) of (4-R, S) 4- (4-formylphenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one in the form of a white powder melting at 181C, ie a yield 40%.

The table below gathers the imidazolinones of formula (XXIV) synthesized:

H ~ HN ~

Position HCO- Yield (%) pF (C) Method J:

The preparation of the compounds of formula (Ig) is now described:

214 ~ 47 Rl N ~) n - R2 Ar2 - X '- NH ~ N`NI - R3 (Ig) in which X 'has the same meaning as before.

s These compounds are obtained by reaction of a 4- (aminophenyl) -2-imidazoline-5-one of formula (XXV) with an electrophilic radical of formula Ar2X '+, such as defined above ~ lellL, according to the reaction scheme:

RJ ~ Y) n-- ~ 2 + RI ~) n - R2 H2N ~ ~ --R3 Ar2 - X '- NH ~ N ~ 3 (xxv) (lg) The reaction is errt ~ ée under the conditions usually practiced for the condensation between the anilines and the various electrophilic compounds. The reaction is carried out in ~ l ~ sence of a base. As a basis we can use the carbonates, alkali or alkaline earth hydroxides, organic bases. The reaction is carried out at a temperature between 20C and 150C, and is conducted in a solvent such as: alcohols, acetonitrile, esters aliphatics, ethers, cyclic ethers, aromatic solvents, chlorinated solvents, dimethylformamide, dimethylsulfoxide, N-methylpyrolidone.
The following example illustrates this process for the preparation of the compounds of formula (Ig).

Fx ~ ple CF9: Preparation of (4-R, S) 4- (4-benzoylaminophenyl) -4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one (compound N 1):

To a solution of 2 g (6.1 mmol) of (4-R, S) 4- (4-aminophenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one and 0.62 g (6.1 mmol) of triethylamine in 50 ml of tetrahydrofuran is added ~, 86 g (6.1 mmol) of benzoyl chloride. Leave to react for 2 hours at ambient temperature, filter the precipitate of triethylamine hydrochloride and then conce., the filtrate under reduced pressure. The crude product is crystallized from diethyl ether. We l ~ clll èr ~ thus 2.47 g (5.7 mmol) of (4-R, S) 4- (4-benzoylaminophenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one (compound N 1) in the state lo of white solid melting at 212 ~ C with a yield of 94%.

The 4- (aminophenyl) -2-imidazoline-5-ones of formula (XXV) are prepared by reduction of 4- (nitrophenyl) -2-imidazoline-5-ones of formula (XXVI). The reduction is carried out according to the usual group reduction methods nitro such as, for example, by catalytic hydrogenation in the presence of a mixture of carbon and palladium (palladium on carbon): F. Melani, L. Cecchi, G. Filacchion. J. Heterocyclic Chem. (1984) Volume 21 page 813, according to diagram:

RI Nq ~ (Y) n - R2 RI Nq ~ Y) n - R2 ~ 3H 2 catalyst ~ X
02N ~. ~ - N - R3 H 2N ~ h ~ N - R3 (XXVI) '(XXV) The following example illustrates this process for the preparation of the compounds of formula (XXV).
2s F: xerr ~ CI15: Preparation of (4-R, S) 4- (4-arninophenyl) 4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one, of structural formula:

\ /

H2N J ~, ~ N ~ NH ~
14 g (39 mmol) of (4-RS) 4- (4-nitrophenyl) 4-methyl-2-methylthio-1-phenylamino-2-irnidazoline-5-one 100 ml of ethyl acetate and 3 g of clla ~ l, palladium on 10% are loaded into a 500 ml autoclave. The autoclave is put s under pressure of 9 bars of hydrogen and heated for 12 hours at 50C. After filtration of the catalyst and concenll ~ tion under reduced pressure one re ~; u ~ èr ~ un yellow honey which crystallizes in ether. After filtration and drying, 11 g are obtained of (4-RS) 4- (4-anlillophéllyl) 4-methyl-2-methylthio-1-phenylarnino-2-irnidazoline-5-one in the form of a yellow solid melting at 194C, i.e. a o lend ~ .l.ent 87%.

By operating in an analogous manner (4-RS) 4- (3-aminophenyl) -4-methyl-2-methylthio-1-phenylamino-2-imidazoline-5-one was obtained with a yield 95% in the form of a yellow solid melting at 100C.

The 4- (nitrophenyl) -2-imidazoline-5-ones of formula (XXVI) are obtained by one of the methods described in European patent application EP 0 551048 published on July 14, 1993 in the case where Y = S and n = 1; according to a process analogous to method C described above ~ l in the case where n equals 1 and Y
means O; either by a process analogous to process D described above "~ nent when n equals 0.

Method K:
2s The preparation of the compounds of formula (Ih) is now described:

Ar2 - (R '12JP -C -Z' - CHR ~ N q (Y) n -R2 R ~ N ~
/ ~ N -R3 (Ih) H

. .

2 ~ 2 ~ '17 in which R '12, p, Z' have the same meaning as above.
These conlL ~ daring are obtained by reacting derivatives of type (XXVII), with an electrophilic agent of formula Ar2- (R '12) p-CO-CI, in ~, lesellce of a base such as an alkali or alkaline earth carbonate or of an organic base in an inert solvent, according to the scheme:

HZ '- CHR ~ N q ~ (Y) n - R2Ar2 - (R 12) P -C - Cl N ~ NR base, solvent WH
(XXVII) Ar2 - (R '1 2) P -C - Z' - CHR 1 ~ 1 N ~ _ (Y) n - R2 ~ `N-R3 (Ih) H

The following example illustrates this process for the preparation of the compounds of lo formula (Ih).

Example CF10: Preparation of (4-R, S) -4- (4- (4-chlorobenzoyloxymethyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-S-one, (compound no 94) with the structural formula:

Cl ~~ /
O NH ~
To a solution of lg (0.0029 mole) of (4-R, S) 4- (4-hydroxymethylphenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in 20 ml of THF
are added to ambient tenlpér ~ t ~ 0.42 ml (0.0029 mol) of triethylamine then 0.38 ml (0.0029 mol) of parachlorobenzoyl chloride. After one half hour of stirring at l ~ llpt: lat ~ re ambient, the medium is hydrolyzed then extract with ethyl acetate. The organic extracts are washed, dried and then evaporated. After mixing with isopropyl ether, we lecu ~: the 0.6 g of (4-R, S) -`- 21426 ~ 7 _ 4- (4- (4-chloroben ~ oyloxymethyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-S-one in the form of a white powder melting at 129C, with a yield of 43%.

The imidazolinone of formula (XXVII) can be prepared according to one of the methods described above.l.ln ~ nt, nolan ~ l-elll by a process similar to that used for the preparation of formula imidazolinone (XXII).

Method L:

The preparation of the compounds of general formula (Ii) is now described:

Ar2 - (R '1 2) P - CR ~ N: ~ (Y) n - R2 (lj) w H 3 in which Ar2, R '12 and Z' have the same meaning as above ~ l ~ ellt.

These compounds are obtained by reacting benzyl derivatives of 2-imidazoline-5-ones of formula (XXVIII) with a nucleophile of formula HZ'R2 optionally in pl ~ sellce of a base such as an alkaline c ~ bonate or alkalize ~ oterrous or organic base according to the scheme:

2 ~ 4 h 6 4 7 p - IR ~ N ~ n - R2 HZ'R

(XXVIII) W base, solvent ZR ~ n - R2 RlNH-R3 w (li) The following example illustrates this process for the preparation of the compounds of formula (Ii).

~ xample CF11: Preparation of (4-R, S) 4- (4- (methoxybenzyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one, (compound # 107) of formula developed:

~ _q S ' N ~ N ~

To a solution of 0.37 g (0.007 mole ~ of sodium methylate in 30 ml of methanol under an inert atmosphere 1.5 g (0.0035 mole) of (4-R, S) 4- are added (4- (chtorobenzyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one. The reaction mixture is heated at 50C for half an hour. After cooled, II, the medium is hydrolyzed and then extracted with ethyl acetate. The organic extracts are washed with a saturated solution of sodium chloride, dried and then evaporated. The crude product thus obtained is then chromatographed on a silica column (eluent: heptane / ethyl acetate 50/50). We get 0, 7 g of (4-R, S) 4- (4- (metho ~ ylJe, ~ yl ~ phenyl) 4-methyl-2-methylthio-1-2 ~ 2 ~ 47 phenylamino 2-imidazoline-5-one in the form of a white powder melting at 161C with 47% yield.

The benzylic derivatives of 2-imidazoline-5-ones of formula (XXVIII) are s pl ~ pa ~ s according to one of the methods described previously, especially in accordance with process analogous to that used for the preparation of the compound of formula (XXIII) from the compound of formula (XXII).

Method M:

The preparation of the compounds of formula (Ij) is now described:

Ar2 - (R '12) P - CR ~ ~ Y) n -R2 XRIN ~ N

(Ij) H

in which R '12 and p have the same meaning as above.nnlenl, Y
replesenle the sulfur atom, X replesenle a halogen atom, preferably a chlorine atom.
These compounds are obtained by halogenation of the compounds of formula (XXIX).
The halogenation is carried out according to methods usually used for this.
type of reaction using hydracid or inorganic acid halide such as SOCl2, PCls, PCl3, POCl3 as cited in Advanced organic chemistry, J.
March, (1985), Page 382, 3rd Edition and according to the reaction scheme:

2 ~ ~ 2647 Ar2 - (R 12) P IR ~, N q - (Y) n ~ R2 OH R ~ /) r N -R3 POX 3 ~ u PX ~ or W. HX or SOCI 2 (XXIX) ~
Ar2 - (R '12) P - CR ~ N q - (Y) n -R2 XRI ~ N;

(Ij) The following example illustrates this process for the preparation of the compounds of FORMULA (U):

Example CF12: Preparation of (4-R, S) -4 ~ (chlorobenzyl) phenyl) -4-methyl-2-methylthio-1-phenylan ~ ino 2-imidazoline-5-one, (compound # 106) of formula developed:

~ S

Y; N ~

To a solution of 6.5 g (0.015 mole) of (4-E?, S) 4- (4 - ((phenyl) hydroxymethyl) phenyl) 4-methyl-2-methylthio-1-phenylarnino 2-imidazoline-5-one in 100 ml of methylene chloride are added to 0C 1.4 ml (0.015 mole) of pyridine then 1.15 ml (0.015 mole) of thionyl chloride. the reaction medium is then brought to reflux for half an hour, then cooled to te.n ~ er ~ ambient ture, hydrolyzed and extracted with methylene chloride. The organic extracts are washed, dried and then evaporated. After mixing the product crude in diisopropyl ether, 4.7 g of (~ R, S) -4- (4-(chlorobenzyl) phenyl) 4-methyl-2-methylthio-1-phenylamino 2-imidazoline-5-one in white powder melting at 153C with a yield of 69%.

~ - 2142 ~

_ 53 The compound of formula (XXIX) is obtained according to one of the methods described previous. ~ e, l ~, no ~ --elll according to the process used for pr ~ a ~ el the compound of formula (XXII).

The following tables bring together the imidazolinones of formula (I), corresponding also to one of the formulas (Ik) or (II) indicated below, which have been l) leL) & l ~ es according to one of the methods which have been described above ~ e - l (indicated in the column c ~ sL ~ undulating).
0 In these tables, the methyl, ethyl, propyl, pyridyl, pyrimidinyl, acetyl, phenyl and benzyl are the ~ ecli ~ / ement, ~ l ~ r ~ senl ~ s by Me, Et, Pr, Py, Pyrim, Ac, Ph, and Bn, and PF means point of ~ sion (PF).

CH 3 Nq ~ (Y ~ n R2 Ar 2 - X ~ `Nll --R 3 (Ik) NW Ar2 ~ (Y) n R3 PF Pro R2 C sold O 4- (PhC (O) NH) SMe Ph 212 J
2 O 4- (PhC (O) NH) OMe Ph 150 C
3 O 4- (4-CI-PhC (O) NH) SMe Ph 219 J
4 O 4- (4-Cl-PhC (O) NH) OMe Ph 182 C
5 O 4- (PhNHC (O) NH) SMe Ph 160 J

6 O 4- (PhNHC (O) NH) OMe Ph 135 C

7 O 4- (PhSO2NH) SMe Ph 185 J

8 O 3-BnO SMe Ph 112 B

`2 ~ 4 ~ 647

9 O 4-BnO OMe Ph 127 C

10 O 4-BnNH SMe Ph 114 J

11 O 4-Bn OMe Ph 148 C

12 O 4-Bn SMe Ph 145 B

13 O 4-BnO SMe 3-F-Ph honey B

14 S4- (2-Phellelhyl) SMe Ph 118 A

15 O4- (4-F-BnO) SMe Ph 167 G

16 o4- (3-F-BnO) SMe Ph 133 G

17 O4- (2-F-BnO) SMe Ph 159 G

18 O4 - [(5-CF3-2-Py) -O] SMe Ph 163 G

19 O4- (4-Me-BnO) SMe Ph 176 G

20 O4- (4-CF3-BnO) SMe Ph 170 G

21 O3- (PhC (O) NH) SMe Ph 130 J

22 O4- (3-Me-BnO) SMe Ph 151 G

23 O4- (2-Me-BnO) SMe Ph 146 G

24 O4- [2,5- (Me) 2-BnO] SMe Ph 149 G

25 O 4-PhS SMe Ph 138 B

26 O 4-PhS SMe 3-F-Ph 118 B

27 O 4-PhS SMe 3-Cl-Ph 95 B

28 O4-1Ph (CH2) 2] SMe Ph 155 B

29 O3- (BnNH) SMe Ph 72 J

30 O4- [4-CI-PhCH (OH)] SMe Ph 94 E

31 O4- ~ PhCH2CH (OH)] SMe Ph 83 E

32 O4- (2-Py-CH20 SMe Ph 139 G

33 O4- ~ PhCH (CH3) 01 SMe Ph 137 G

34 O4- (4-Py-CH20) SMe Ph 215 G

2 ~ 42 ~ 47 O4- (3-Py-CH20) SMe Ph 138 G
36 O4- (5-CF3-2-PyO) OMe Ph 88 C
37 O4- (PhNHC (O) O) SMe Ph 201 G
38 O4-1PhS (O)] SMe Ph 132 B
39 o4- [PhS (O)] SMe 3-CI-Ph 164 B
O4- [PhS (O)] SMe 3-F-Ph 115 B
41 O4- (PhS02) SMe Ph 80 B
42 O4- [Ph (CH2) 2] OMe Ph 100 C
43 O4- (PhC02) SMe Ph 170 G
44 OPhCOCH2O SMe Ph 163 G
O4- [4-CI-PhNHC (O)] SMe Ph 210 H
46 O4- [PhNHC (O)] SMe Ph 105 H
47 O4- (2,4-diF-PhOCH2) SMe Ph 152 48 O4- (3-CI-PhNHCO) S-Me Ph 115 H
49 O4- (4-CI-PhCMe (OH)) S-Me Ph 90 E
O4- (2- (4,6-diMe- S-Me -Ph 87 G
Pyrim) O) 51 O4- (2-Me-PhCH20) S-Me Ph 129 G
52 O4- (PhSO2) S-Me 3-CI-Ph 153 B
53 O4- (PhSO2) S-Me 3-F-Ph 188 B
54 O4- (PhS) And Ph 85 D
56 O4- (PhOCH2) MeS Ph 153 57 O4- (4-CI-PhOCH2) MeS Ph 164 58 O4- (3-CI-PhOCH2) MeS Ph 149 59 O4- (2-CI-PhOCH2) MeS Ph 102 O4- (4-F-PhOCH2) MeS Ph 132 2 ~ 42647 61 O4- (3-F-PhOCH2) MeS Ph 147 62 O4- (2-MeO-PhOCH2) MeS Ph 156 63 O3- (PhCH2O) MeO Ph 56 C
84 O3- (PhCH2O) OMe Ph 56 C
O4- (2-F-PhOCH2) SMe Ph 153 86 O 4-PhSO And Ph honey D
87 O4-PhSO2 And Ph 194 D
88 O4- (4-F-PhC (O)) SMe Ph 163 E
89 O4- (4-MeO-Ph) OCH2 SMe Ph 151 O4- (3-MeO-Ph) OCH2 SMe Ph 131 91 O4- (4-CF3-Ph) OCH2 SMe Ph 173 92 O4- (3-MeO-PhCH2O) SMe Ph 126 G
93 O4- (2-F-PhOCH2) OMe Ph 165 C
94 O4- (4-CI-PhCO2CH2) SMe Ph 129 K
O 4-PhSO OMe Ph honey C
96 O4- (4-CI-Ph) CH2O SMe Ph 187 G
98 O4-PIICH (OH) SMe Ph honey E
99 O4- (4-MeO-PhCH20) SMe Ph 156 G
100 O4- (4-NC-PhCH20) SMe Ph 209 G
101 O4-PhOCH2 OMe Ph 158 C
102 O4- (3-Cl-PhOCH2) OMe Ph 147 C
103 O4- (3-F-PhOCH2) OMe Ph 179 C
104 O4- (4-F-PhOCH ~) OMe Ph 141 C
105 O4- (4-cF3-pllocH2) OMe Ph 143 C
106 O4-PhCH (Cl) SMe Ph 153 M
107 o4-PhCH (OMe) SMe Ph 161 L

2 ~ 2 ~ 47 108 O4-PhCH (OMe) OMePh 136 C
109 O4-PhS SMe2,5-diF-Ph 104 B
110 O4-PhCO SMePh 162 E
111 O4- (2-CN-PhCH2O) SMePh 174 G
112 O 4-PhCO OMePh 83 C
113 O3- (4-Cl-PhCOOCH2) SMePh 156 K
114 O3- (4-CI-PhCOOCH2) OMePh 105 C
115 O4-PhS SMe2,3-diF-Ph 113 B
116 O4- (3-CN-PhCH20) SMePh 171 G
117 O3- (4-CF3-PhOCH2) SMePh 127 118 O3- (PhCO) SMePh 149 E
119 O3- (4-Cl-PhCH (OH)) SMePh 156 E
120 O3- (4-CI-PhOCH2) SMePh 112 121 O3- (4-CF3-PhOCH2) OMePh 102 C
122 O3- (PhCH (OMe)) OMePh 120 C
123 O3- (4-CI-PhCH (OMe)) OMePh 120 C
124 O 3- (4-CI-PhOCH2) OMe Ph honey C
125 O3- (4-Me-PhOCH2) SMePh 87 126 O3- (4-F-PhOCH2) OMePh 136 C
127 O3- (4-F-PhCH (OH)) SMePh 128 E
128 O3- (4-CF3-PhCH (OH)) SMePh 145 E
129 O3- (4-OMe-PhCH (OH)) SMePh 114 E
130 O3- (4-F-PhCH (OMe)) OMePh 131 C
131 O3- (PhCH2O) SMePh 132 132 O 3- (PhCO) SMePh honey E
133 O 3- (PhOCH2) OMePh honey C

`- 2142 ~ 47 134 O4- (4-FPhCH2O) OMe Ph 171 G
135 O4 - [(2-Benzothiazolyl) O] SMe Ph 144 G

R ~ NH ~

Ar2 /
(He) N Ar2 R PF C Process 64 4-F-Ph NO2 171 F
Ph NO2 148 F
66 2-F-Ph NO2: 115 F
67 3-F-Ph NO2 112 F
68 4-Cl-Ph NO2 146 F
69 3-Cl-Ph NO2 103 F
2-Cl-Ph NO2 93 F
712-Naph ~ yl NO2 131 F
72 2-OH-Ph NO2 97 F
73 4-HOPh NO2 145 F
74 4-MeOPh NO2 134 F
75 3-MeOPh NO2 165 F

214; ~ 6 17 76 4-MePh NO2 115 F
77 2-MePh NO2 120 F
78 3-MePh NO2 113 F
79 Ph CF3 166 F
80 4-Me-Ph CF3 149 F
814-MeO-Ph CF3 151 F
82 4-CI-Ph CF3 149 F
83 3-F-Ph CF3 143 F

The object of the plesellle invention is some of the new compounds described ptécéden ~ llelll as intermediates, namely the compounds of formulas IIIa, IIIb, IV, VII, XIII, XIX, XX, XXII, XXIV, and XXVII in which the substituents have the meaning defined above. As compounds defined by the general formula (I) of the invention, these compounds may exist in one or more isomeric forms depending on the number of centers asymmetric of the molecule. The invention therefore relates equally to all optical isomers of the usable compounds col ~ R intermediates than their racemic mixtures and the corresponding diastereoisoneles, separate or in mix, and notallullent enantiomers of compounds comprenalll carbon asymmetrical carrier of Rl. Separation of optical isomers and / or diastereoisomers from racemic mixtures can be carried out according to methods known per se. Enantiomers of intermediate compounds conl ~, lcnant asymmetric carbon carrying Rl can also be prepared according to methods known per se or according to the methods described precedcllùnenl, from chiral raw materials, and noLanlmc.ll from a chiral amino acids of formula (IX), that is to say from the compounds of formula (IX) in which the calbolle attached to R1 is a carbon asymmetric.

The invention also relates to a method for treating plants.
cultivated affected or likely to be affected by fungal diseases characterized in that an effective dose of a compound according to formula (I) is applied to the aerial parts of these plants. By effective dose is meant a quantity surllsal ~ te for p ~, l.,. etlle control and destruction of mushrooms ~ sellls on these cultivated plants. Use doses can however vary within wide limits depending on the fungus to be controlled, the type of crop, the climatic conditions, and according to the compound used.
In practice, the compounds are advantageously applied to doses of 0.002 to 5 kg / ha, and preferably 0.005 to 1 kg / ha.
By fungal diseases is meant diseases caused by 0 phytopathogenic fungi, especially those of the oolllycetes family, ascomycetes and basidiomycetes.
Among the crops that can be treated with fungicide using a compound according to the invention, mention may be made of rice, cereals, nola..l, ~ .ellt wheat and barley, as well as vegetable plants. Rice is a preferred crop for fungicide treatments using a compound according to The invention.

The following examples illustrate the good fungicidal activity of compounds according to the invention.
F.xe ~ le Rl: In vivo test on Pyricularia oryzae responsible for rice piriculariosis:

An aqueous suspension of the active material is prepared by fine grinding 2s to be tested having the following composition:
- active ingredient: 60 mg.
- acetone: 5 ml - surfactant (oleate of polyoxyethylene derivative of sorbitan) diluted 10% in water: 0.3 ml - make up to 60 ml of water.
This aqueous suspension is then diluted with water to obtain the desired concentration of active ingredient.
Rice, sown in pots in a 50/50 mixture of enriched peat and pozzolan, is treated at the stage of about 10 cm in height (which is ~ olld at 2-3 leaf stage) by spraying the above aqueous suspension.

`- 214 ~ 47 After 24 hours, a suspension is applied to the leaves.
aqueous spore of Pyric ~ ria oryzA ~ obtained from a culture of 15 days, then suspended at 100,000 units per cm3.

The rice plants are placed for 24 hours in incubation (25C, 100% relative humidity), then put in observation cell, in the same conditions, for 5 days.
Reading is done 6 days after the contamination.
Under these conditions, good protection is observed at a dose of I g / l.
(at least 75%) or total with the following compounds: 9, I l, 15, 16, 23, 27 to 29, 31 to 33, 35 to 37, 42, 67, 68, 84, 92, 94, 95, 96, 102, 104, 105, 108, 109, 112, 114, 121.

Fx.orrtple R2: In vivo test on Puccinia reco ~ ldita responsible for wheat rust:

An aqueous suspension of the material is prepared by fine grinding active to be tested having the following composition:
- active ingredient: 60 mg - acetone: 5 ml - surfactant ~ Tween 80, (oleate of polyoxyethylenated derivative of sorbitan) diluted 10% in water: 0.3 ml - make up to 60 ml of water.
2s This aqueous suspension is then diluted with water to obtain the desired concentlation in active matter.

Wheat sown on a 50/50 pozzolan peat substrate in a bucket and maintained at 12 C, is treated at the 10 cm height stage by spraying of the above aqueous suspension.
After ~ 4 hours, an aqueous suspension of spores (100,000 sp / cm3) is sprayed onto wheat; this suspension was obtained from contaminated plants. The wheat is then placed in the cell for 24 hours incubation at around 20C and 100% relative humidity, then for 7 to 14 days at 60% relative humidity.

2142 ~ 7 The control of the state of the plants is ~ between the 8th and the 15th day after the cont ~ min ~ tion, by comparison with an untreated control.
In these conditions, protection is observed at a dose of 1 g / l good (at least 75%) or total with the following compounds: 4, 8 to 13, 15 to 18, 20 to 28, 31 to 33, 35, 36, 38, 40 to 43, 48, 49, 73, 79, 81, 84, 85, 89, 90, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 115, 116, 117, 119, 120, 121.

lo F.xelT ~ le P ~ 3: In vivo test on Septoria ~ ri ~ here responsible for the wheat septoria:

An aqueous su ~ l.ellsion, concentration 1 gtl, of the active ingredient tested is obtained by grinding 60 mg of it in the following mixture:
s - acetone: S ml surfactant (polyoxyethylenated derivative of sorbitan oleate) diluted to 10%: 0.3 ml then the volume is adjusted to 60 ml with water.
This aqueous suspension is then diluted with water to obtain the desired concentration of active ingredient.
Wheat plants (variety Darius), sown on a peat substrate-pou ~ zolane 50/50 and grown in a greenhouse at temperature 10-12 C, are treated at the stage I sheet (size about 10 cm) by spraying the material suspension active described above.
Plants, used as controls, are treated by spraying a aqueous solution not containing the active ingredient.
24 hours after treatment, the plants are contaminated by spraying of an aqueous suspension of spores (500 OOOsp / ml) harvested from an aged culture 7 days.
After contamination, the plants are placed at I ~ C in an atmosphere wet. The grading is carried out 20 days after contamination in comparison with the control plants.
Under these conditions, good protection is observed at the dose of I g / l.
(at least 75%) or total with the compounds: 9, 15, 21, 23, 32, 36, ~ 19, 73, 88.3s 89, 90, 93, 94, 95, 98, 104, 105, 108, 112, 114, 117, 118, 120, 121.

2 ~ 426 ~ 7 The plesellte invention also relates to compositions, usable as fungicidal agents, containing as active ingredient (s) a (or more) compound according to formula (I) as described above ~ llelll, s mixed with solid or liquid supports, acceptable in agriculture and surfactants also acceptable in agriculture. In particular are the inert and usual SUPIJOILS and the usual surfactants can be used.
These compositions can also contain all kinds of other ingredients such as, for example, protective colloids, adhesives, thickeners, thixotropic agents, penetrating agents, stabilizers, sequestering agents, etc. More generally the compounds used in the invention can be combined with any solid or liquid additive that meets the usual techniques of formulation formulation.
In general, the compositions according to the invention contain s usually from 0.05 to 95% approximately (by weight) of a compound according to the invention (hereinafter called active ingredient), one or more solid supports or liquids and, optionally, one or more surfactants.
By the earth "support", in the present description, we mean a material organic or mineral, natural or synthetic, with which the compound is combined to facilitate its application on the plant, on seeds or on ground. This support is therefore generally inert and it must be acceptable in agriculture, especially on the treated plant. The support can be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, etc.) or liquid (water, alcohols, in particular butanol etc ...).
The surfactant can be an emulsifying, dispersing or wetting agent of ionic or nonionic type or a mixture of such agents surfactants. Mention may be made, for example, of salts of p ~ lyacrylic acids, of salts lignosulfonic acids, salts of phenolsulfonic acids or naphthalenesulfonic, polycondensates of ethylene oxide on alcohols fatty or fatty acids or fatty amines, substituted phenols (note ~ lel ~ l of alkylphenols or arylphenols), salts of acid esters sulfosuccinics, taurine derivatives (including alkyltaurates), phosphoric esters of polyoxyethylated alcohols or phenols, fatty acid and polyol esters, sulfate, sulfonate and phosphate derivatives of previous compounds. The plesence of at least one surfactant is -21 ~ 26 ~ 7 -generally essential when the compound and / or the inert support are not not soluble in water and that the vector of the application is water.
Thus, the compositions for agricultural use according to the invention can contain the active ingredients according to the invention within very wide limits, ranging from 0.05% to 95% (by weight). Their surfactant content is advantageously con, l, ~ ise between 5% and 40% by weight.
These compositions according to the invention are themselves under forms quite diverse, solid or liquid.
As forms of solid compositions, mention may be made of powders for o dusting (with compound content of up to 100%) and granules, note ... l..ellt those obtained by extrusion, by compaction, by inlplégnation of a granulated support, by granulation from a powder (the content of compound in these granules being between 0.5 and 80% for the latter cases), the col .. ~ néou or effervescent tablets.
The co-poses of formula (I) can also be used in the form of powders for dusting; it is also possible to use a composition containing 50 active ingredient and 950 g of talc; we can also use a composition co.nlJlenant 20 g of active material, 10 g of finely divided silica and 970 g of detalc; these components are mixed and ground and the mixture is applied by powdering.

As forms of liquid compositions or intended to constitute liquid compositions during application, there may be mentioned the solutions, in particularly water-soluble concellles, emulsifiable concentrates, emulsions, suspensions concen ~ l ~ es, aerosols, wettable powders (or spray powder), pasta, gels.
The concel "emulsifiable or soluble cc, l..premlel1t most often 10 to 80% of active ingredient, emulsions or solutions ready for application containing, for their part, 0.001 to 20% of active material.
In addition to the solvent, the emulsifiable substances may contain when it is nPcess ~ ire, 2 to 20% of appropriate additives such as stabilizers, surfactants, penetration agents, corrosion inhibitors, the above dyes or adhesives.,., ncnt mentioned.

`- 2 ~ 42 ~

From these designs, it can be obtained by dilution with water emulsions of any desired concentration, which are particularly suitable for application on crops.
As an example, here is the composition of some concelllres emulsifiable:

Fxen ~ ple CF 1:
- active ingredient 400 g / l - alkaline dodecylbenzene sulfonate 24 g / l o - oxyethylated nonylphenol with 10 molecules ethylene oxide 16 g / l - cyclohexanone 200 g / l - aromatic solvent qsp1 Iitre According to another formula of emulsifiable composition, we use:

F.xen ~ CF. 2 - active ingredient 250 g - epoxidized vegetable oil 25 g - mixture of alkylaryl sulfonate and polyglycol ether and fatty alcohols 100 g - dimethylformamide -50 g - xylene 575 g The concel1tl ~ es suspensions, also applicable in spraying, are prepared so as to obtain a stable fluid product which does not deposit and they usually contain 10 to 75% active ingredient, 0.5 to 15 % of surfactants, from 0.1 to 10% of thixotropic agents, from 0 to 10%
applied additives, such as defoamers, corrosion inhibitors, stabilizers, penetrating agents and adhesives and, as a carrier, water or an organic liquid in which the active ingredient is little or not soluble: some organic solids or mineral salts may be dissolved in the support to help prevent sedimentation or as antifreeze for water.

. - 214 ~ G47 As an example, here is a composition of suspension concenll; e:

Fx ~ n ~ SC 1:
- active ingredient 500 g s - polyethoxylated tristyrylphenol phosphate 50 g - polyethoxylated alkylphenol 50 g - sodium polycarboxylate 20 g - ethylene glycol 50 g - organopolysiloxane oil (antifoam) 1 g o - polysaccharide 1.5 g - water 316.5 g Wettable powders (or spray powder) are usually prepared so that they contain 20 to 95% active ingredient, and they s usually contain, in addition to the solid support, from 0 to 30% of an agent wetting, from 3 to 20% of a dispersing agent, and, when necessary, from 0.1 to 10% of one or more stabilizers and / or other additives, such as penetration agents, adhesives, or agents anti-caking agents, dyes, etc ~
To obtain sprayable powders or wettable powders, hltillle mixture ~ the active ingredients in the applol mixers, ~ iés avec les additional substances and we grind with mills or other grinders applol, bound This gives spraying powders whose wettability and suspension are advantageous; we can suspend them with water to any conce, ~ llation desired and these suspensions are usable very advantageously in particular for the application to the leaves of plants. Instead of wettable powders, it is possible to make pasta. The terms and conditions for making and using this pasta are similar to wettable powders or spray powders.
As an example, here are various compositions of wettable powders (or spraying powders):

Fx ~ n ~ PM 1 - active ingredient 50%
- ethoxylated fatty alcohol (wetting agent) 2.5%
- ethoxylated phenylethylphenol (dispersing agent) 5%

214 ~ 547 - chalk (inert support) 42.5%

P.xP ~ PM 2:
- active ingredient 10%
s - synthetic oxo ramo type ~ ram, in C13 ethoxylated by 8 to 10 ethylene oxide (wetting agent) 0.75%
- lignosul ~ neutral calcium onate (agent dispersant) 12%
lo - calcium carbonate (inert chatge) qs 100%

Fx ~ n ~ ple PM 3:
This wettable powder conlielll the same ingredients as in the previous example, in the following options:
Is - active ingredient 75%
- wetting agent 1.50%
- dispersing agent 8%
- carb ~ calcium nate (inert filler) qs 10 ~%

Fxernple PM 4:
- active ingredient 90%
- ethoxylated fatty alcohol (wetting agent) 4%
- ethoxylated phenylethylphenol (dispersing agent) 6%

2s Fx ~ n ~ ple PM S:
- active ingredient . 50%
- mixture of anionic surfactants and non-ionic (wetting agent) 2.5%
- sodium lignosulfonate (dispersing agent) 5%
- kaolin clay (inert support) 42.5%

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder or a concellllé with water emulsifiable according to the invention, are con ~ l) read in the general framework of the 3s plesenle invention. The emulsions can be of the eal ~ years-oil type or -~ 26 17 oil-in-water and they can have a thick consistency like that of a "mayonnaise".
The compounds according to the invention can be formulated in the form of granules available in water also included within the scope of the invention.These dispersible granules, of apparent density generally included between about 0.3 and 0.6 have a particle size generally comprised between about 150 and 2000 and preferably between 300 and 1500 microns.
The active ingredient content of these granules is generally understood between about 1% and 90%, and preferably between 25% and 90%.
0 The rest of the granule is essentially composed of a solid filler and optionally surfactant adjuvants giving the granule properties of dispersibility in water. These granules can be essentially two distinct types depending on whether the charge selected is soluble or not in water.
When the filler is water-soluble, it can be mineral or, preferably, 1S organic. Excellent results have been obtained with urea. In the case of a insoluble filler, this is preferably mineral, such as for example the kaolin or benlollile. It is then advantageously accompanied by agents surfactants (2 to 20% by weight of the granule) of which more than half is, for example, constituted by at least one dispersing agent, essentially anionic, such as an alkaline or alkaline earth polynaphthalene sulfonate or a alkali or alkaline earth lignosulfonate, the remainder consisting of nonionic or anionic wetting agents such as an alkyl naphthalene sulfonate alkaline or alkaline earth.
Furthermore, although it is not essential, we can add other adjuvants such as defoamers.
The granule according to the invention can be prepared by mixing necessary ingredients then granulation according to several techniques per se known (bezel, fluid bed, atomizer, extrusion, etc.). We terrnine generally by crushing followed by tarmisage to particle size chosen in the lirnites mentioned above. We can still use granules obtained as plecédelnll.tnl then impregnated with a composition containing the active ingredient.
Preferably, it is obtained by extrusion, operating as indicated.
in the examples below.
3s ~, F.xen ~ ple Gnl: Gr ~ nnlés tli. ~ Persibles In a mixer, 90% by weight of active material is mixed and 10% urea pearls. The mixture is then ground in a pins. A powder is obtained which is moistened with approximately 8% by weight s of water. The wet powder is extruded in a perforated roller extruder.
A granule is obtained which is dried, then crushed and sieved, so as not to keep the ~;, peclive ~ that the granules with a dimension between 150 and 2000 microns.

Fx ~ le Gn2: Gram-les ~ li.c ~ ersibles In a mixer, ~ n mixes the following constituents:
- active ingredient 75%
- wetting agent (sodium alkylnaphthalene sulfonate) 2%
- dispersing agent (sodium polynaphthalene sulfonate) 8%
IS - inert filler insoluble in water (kaolin) 15%

This mixture is granulated in a fluid bed, in plesellce of water, then dried, crushed and sieved so as to obtain granules of mixed dirnension between 0.15 and 0.80 mm.
These granules can be used alone, in solution or dispersion in water in order to obtain the desired dose. They can also be used to prepare combinations with other active ingredients, note-lnlelll fungicides, the latter being in the form of wettable powders, or granules or sl ~ aqueous pellsions.
2s With regard to the compositions suitable for storage and transport, they more advantageously contain from 0.5 to 9% (by weight) of active substance.

Claims (20)

1. Compounds derived from 2-imidazoline-5-ones, characterized in that they meet the general formula (I):

in which:

- R1 represents a hydrogen atom, or a vinyl or allyl group, or a alkyl or haloalkyl radical, each of 1 to 3 carbon atoms;
or, R1 and Ar2-X-Ar1 can also form, with the carbon to which they are linked on the imidazolinone cycle, the following motif:

in which the bold point represents the carbon of the imidazolinone ring of formula (I) to which the radicals R1 and Ar2-X-Ar1 are linked, and m equals 2, 3 or 4;

-n = 0 or 1;

- Y represents the oxygen or sulfur atom;

- R2 represents:
- the hydrogen atom when n equals 0 or - an alkyl or haloalkyl group, each of 1 to 3 carbon atoms or cyclopropyl group;

R3 represents an aryl or heteroaryl radical comprising phenyl, naphthyl, pyridyle, pyrimidyle, pyridazinyle, pyrazinyle, thiazolyle, benzothienyle, benzofuryl, quinolinyl, isoquinolinyl, benzothiazolyl or methylene dioxyphenyl, each of these radicals being optionally substituted with 1 to 7 groups, preferably from 1 to 3 groups, chosen from meanings of R5 defined below;

-R4 represents a hydrogen atom, a formyl or aroyl radical, a radical acyl of 2 to 6 carbon atoms, an alkoxycarbonyl radical of 2 to 6 atoms of carbon, an aryloxycarbonyl or arylsulfonyl radical, a radical alkylsulfonyl of 1 to 6 carbon atoms, or an alkyloxalyl radical or alkoxyoxalyl of 3 to 6 carbon atoms;

- R5 represents:
a halogen atom or the hydroxy group, mercapto, nitro, SF5, cyano, thiocyanato or azido; or an alkyl, haloalkyl, cyanoalkyl, alkoxy, haloalkoxy radical, cyanoalkoxy, alkylthio, haloalkylthio, cyanoalkylthio, alkylsulfinyle, alkylsulfonyl, haloalkylsulfinyl or haloalkylsulfonyl, each from 1 to 6 carbon atoms; or a cycloalkyl, halocycloalkyl, alkenyl, alkynyl, alkenyloxy radical, alkynyloxy, alkenylthio, alkynylthio, each of 3 to 6 carbon atoms ; or an amino radical optionally mono or disubstituted by a radical alkyl or acyl of 1 to 6 carbon atoms or alkoxycarbonyl of 2 to 6 carbon atoms; or - an alkoxycarbonyl group of 2 to 7 carbon atoms; or - an N-alkylcarbamoyl group of 2 to 7 carbon atoms; or - an N, N-dialkylcarbamoyl group of 3 to 13 carbon atoms;

- W represents O, S or SO;

- Ar1 is a divalent radical which derives from an aryl or heteroaryl radical comprising the phenyl, naphthyl, thienyl, furyl, pyrrolyl, pyridyl radicals, benzothienyl, benzofuryl, indolyl, quinolinyl, isoquinolinyl, or methylenedioxyphenyl, each of these radicals being optionally substituted by 1 to 6 groups, preferably by 1 to 3 groups, chosen from meanings of R5;

- Ar2 represents a mono or bicyclic system of 5 to 10 atoms, which is aromatic, saturated or unsaturated, and which is either a carbocyclic system or a heterocyclic system containing from 1 to 4 heteroatoms chosen from O, S, or N, and which includes phenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, thienyl, furyl, pyrrolyl, pyridyl, benzothienyl, benzofuryl, indanyl, indolyl, quinolinyl, isoquinolinyl, methylenedioxyphenyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, isoxazolyle, thiazolyle, isothiazolyle, oxadiazolyle, thiadiazolyle, benzimidazolyle, indazolyle, benzoxazolyle, benzisoxazolyle, benzothiazolyle, benzisothiazolyle, pyrimidyle, pyrazinyle, pyridazinyle, triazinyle, naphtyridyle, quinoxazolyl, quinazolyl, cinnolyl or phthalazinyl, each of these radicals being optionally substituted with 1 to 7 groups, preferably 1 to 3 groups, chosen from the meanings of R5;

- X represents a sequence of general formula:

in which:
- j and k, identical or different, are equal to 0 or 1;
- R "and R ', identical or different, represent a chain hydrocarbon, saturated or unsaturated, which contains from 1 to 6 atoms of carbon, optionally substituted by 1 to 12 groups, of preferably by 1 to 3 groups, chosen from R7 defined above after; and in which one or more carbon atoms may be replaced by O, S, N (R6), R6 being defined below;
- A represents O, S, N (R6), SO, SO2, CO, CS ,, Si (R8) (R'8), N2, C (R10) (R'10), or or in which Z represents O, S, C (R11) (R'11); R8 to R11 being defined below;

- R6 represents:
- a hydrogen atom or a cyano, hydroxy group, amino, formyl, morpholino, piperidino, pyrrolidino, piperazino, or - an alkyl, haloalkyl, cyanoalkyl, alkoxy radical, haloalkoxy, cyanoalkoxy, alkylsulfonyl, haloalkylsulfonyl, cyanoalkylsulfonyl, each comprising from 1 to 6 carbon atoms, or - a monoalkylamino or dialkylamino radical, or - a cycloalkyl, halocycloalkyl, alkenyl radical, alkynyl, alkenyloxy, alkynyloxy, each 3 to 6 atoms of carbon; or - an acyl or alkoxycarbonyl radical, each from 2 to 6 carbon atoms; or - a carbamoyl radical (optionally substituted by a or two alkyl radicals) of 1 to 7 carbon atoms or sulfamoyl of 1 to 6 carbon atoms; or - an aroyl or arylsulfonyl radical; or - an alkyloxalyl or alkoxyoxalyl radical, each from 3 to 8 carbon atoms; or - an oxamyl radical (optionally substituted by one or two alkyl radicals) of 2 to 8 carbon atoms - R7 represents a halogen atom, a cyano group, thiocyanato, hydroxycarbonyl, amino (optionally substituted), hydroxyl, oxo, alkoxy, alkoxycarbonyl, haloalkoxy, alkoxyalkoxy, thiol, alkylthio, haloalkylthio, alkoxyalkylthio, acyloxy, alkyl, haloalkyle, alkoxyalkyle, alkylidene, aroyloxy, heteroaroyloxy, arylacyloxy, cycloalkylcarbonyloxy, acylthio, aroylthio, heteroaroylthio, arylacylthio, cycloalkylcarbonylthio, carbamoyloxy (optionally substituted), carbamoylthio (optionally substituted), thiocarbamoyloxy (optionally substituted), dithiocarbamoyl (optionally substituted), acylamino, cycloalkylcarbonylamino, aroylamino, ureïdo (optionally substituted), thiouréïdo, alkoxycarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, aminosulfonylamino (optionally substituted), it being understood than:
- optionally substituted means radicals optionally substituted by one or two alkyl radicals, - each aliphatic hydrocarbon radical has from 1 to 4 carbon atoms, and;
- the cycloalkyl radical contains from 3 to 7 atoms of carbon;

- R8 and R'8, identical or different, represent:
- an alkyl radical of 1 to 6 carbon atoms; or - a cycloalkyl radical of 3 to 7 carbon atoms; or - an alkenyl, alkynyl radical of 2 to 6 atoms of carbon; or - an arylalkyl radical, preferably benzyl, or a optionally substituted aryl radical, preferably phenyl optionally substituted with 1 to 5 groups, preferably by 1 to 3 groups, chosen from meanings of R5;

- R9 represents:
- the hydrogen atom, or a morpholino group, piperidino, pyrrolidino, piperazino; or - an alkyl, haloalkyl, cyanoalkyl, alkoxy radical, haloalkoxy, cyanoalkoxy, alkylthio, haloalkylthio, cyanoalkylthio, each of 1 to 6 carbon atoms or dialkylamino containing from 2 to 6 carbon atoms;

- R10 and R'10, identical or different, represent the atom of hydrogen or an alkoxy group containing 1 to 6 atoms of carbon or R7;

- R11 and R'11, identical or different, represent the atom hydrogen or halogen or an alkyl group of 1 to 3 atoms of carbon;

as well as the salified forms, and the enantiomers and stereoisomers of these compounds, especially the 2 enantiomers of each of these compounds corresponding to the asymmetric carbon of the imidazolinone ring carrying R1;

and with the exception of compounds for which:
- when (Y) n-R2 represents methylthio, methyl or ethyl, Ar2-X-Ar1 represents an optionally substituted phenoxyphenyl group;
- when (Y) n-R2 represents a methoxy, when R1 is a methyl, when R3 represents a phenyl or pyridyl radical, optionally substituted by a fluorine atom or a methyl group, when R4 is hydrogen, and when W represents an oxygen atom, then Ar2-X-Ar1 represents either a 4-phenoxyphenyl group, optionally substituted on its phenoxy part by 1 or 2 fluorine atoms, namely the 3-phenoxyphenyl group;

and with the exception of the compound of formula:

2. Compounds according to claim 1, characterized in that:

- Ar1 represents a divalent radical derived from a phenyl, naphthyl, thienyl, pyridyl, benzothienyl, quinolinyl, each of these radicals being optionally substituted by 1 to 3 groups, chosen from the meanings of R5;
- Ar2 represents a phenyl, naphthyl, thienyl, pyridyl radical, benzothienyl, thiazolyl, benzothiazolyl, pyrimidyl, each of these radicals being optionally substituted by 1 to 3 groups, chosen from among meanings of R5. 3. Compounds according to claim 1, characterized in that than:
- Ar1 represents a divalent radical derived from a phenyl, thienyl, pyridyle, optionally substituted by 1 to 3 groups chosen from a halogen atom, an alkyl or haloalkyl radical;
- Ar2 represents a phenyl, naphthyl, pyridyl radical, benzothiazolyle, optionally substituted by 1 to 3 groups chosen from a halogen atom, an alkyl or haloalkyl radical;
- X represents the sequence of general formula:
- (R ") jA- (R ') k-in which:
- R "and R ', identical or different, represents a chain carbonaceous of 1 to 3 carbon atoms, preferably a methylene group, in which a carbon atom is optionally replaced by O or NH, and which is optionally substituted by 1 to 3 groups chosen from an atom halogen, hydroxyl, oxo or C1-C3 alkyl radical;
- A is O, S, SO, SO2, CO, C (R10) (R'10), or wherein:
- R10 and R'10, identical or different, are a hydrogen atom, halogen, hydroxyl, C1-C3 alkyl or C1-C3 alkoxy;
- Z represents O or C (R11) (R'11), where R11 and R'11, identical or are a hydrogen or chlorine atom. 4. Compounds according to claim 1, characterized in that that they correspond to formula I in which simultaneously:
- R1 is a methyl radical;
- R2 is a methyl or ethyl radical;
- R3 represents a phenyl or pyridyl radical;
- R4 is a hydrogen atom or a formyl radical;
- R5 is a halogen atom or a C1-C3 alkyl or C1-C3 radical haloalkyl; and - W is an oxygen atom. 5. Process for the preparation of the compounds of formula (I) according to the claim 1, in which R4 is different from the hydrogen atom, by reaction of the compounds of formula la with a compound of formula R4L ', in presence of a base and in a solvent medium, according to the diagram:

R4L ' (Ia) (I) in which :
- R4 represents the formyl radical, an acyl group of 2 to 6 atoms of carbon, aroyl, alkoxycarbonyl of 2 to 6 carbon atoms, aryloxycarbonyl, alkylsulfonyl, arylsulfonyl, or an alkyloxalyl radical or alkoxyoxalyl of 3 to 6 carbon atoms;
- L 'represents:
a halogen atom, preferably chlorine, bromine or iodine, the sulfate group, an aryloxy or arylthio radical, optionally substituted, of preferably phenoxy, an alkoxy or dialkylamino radical, an R4O group when R4 is an acyl or arylsulfonyl group or alkylsulfonyl. 6. Method according to claim 5, characterized in that one uses as a base a strong base such as an alkali hydride or hydroxide or alkaline earth metal, alcoholate or tertiary amine, in that the reaction is performed at a temperature between -30 ° C and + 50 ° C and in that the solvent is chosen from cyclic or non-cyclic ethers, the dimethylformamide, dimethyl sulfoxide, acetonitrile or a solvent aromatic. 7. Process for the preparation of the compounds of formula (II) by S-alkylation 2-thiohydantoins of formula (III), in the presence of a base and in a solvent, according to the diagram:

Based solvent (III) (II) in which R1, R2, R3, Ar1, Ar2, X are defined according to claim 1, W
represents S or O, and L represents a group chosen from an atom halogen (preferably chlorine, bromine, or iodine), or the sulfate group, alkylsulfonyloxy, or arylsulfonyloxy. 8. Process for the preparation of the compounds of formula (IIa), characterized in which is reacted successively, in the presence of a solvent, the compound of formula (VII) with a hydrazine of formula R3-NH-NH2, then with a base of formula B-M +, and finally with an alkylating agent of formula R2L, according to the diagram:

(VII) R2L (IIa) in which R1, R2, R3, Ar1, Ar2, X are defined according to claim 1, with the restriction that R2 is different from the hydrogen atom, RE represents a C1-C3 alkyl radical, and L is a halogen atom or the alkyl sulphate group, alkylsulfonyloxy or arylsulfonyloxy. 9. Method according to claim 8, characterized in that the base is chosen from an alkaline or alkaline earth alcoholate, an alkali hydroxide or alkaline earth, or a tertiary amine, and in that the reaction is carried out a temperature between -10 and + 80 ° C and in a chosen solvent in particular among a cyclic or non-cyclic ether, an alcohol, an ester, the DMF, DMSO, acetonitrile or among an aromatic. 10. Process for the preparation of the compounds of formula (XI), characterized in that the 2-alkylthio-2-imidazoline-5-ones of formula (II) with an alcohol R2OH in the presence of a strong base and in a solvent, according to the diagram:

Based solvent (II) (XI) in which R'2 represents an alkyl group comprising from 1 to 3 atoms of carbon and the other groups are defined according to claim 1. 11. Method according to claim 10, characterized in that the reaction is practiced in R2OH alcohol, as a solvent, and using alcoholate sodium R2O-Na + as base, and in that the reaction is carried out at a temperature between 20 and 80 ° C. 12. Process for the preparation of the compounds of formula (XII):

(XII) characterized in that a hydrazine of formula R3-NH-NH2 is reacted with an azalactone of formula (XIII), according to the scheme:

CH3COONa (XIII) (XII) in which R1, R2, R3, Ar1, Ar2 and X are defined according to claim 1, by heating the mixture of reagents in acetic acid to reflux, in the presence sodium acetate as a catalyst. 13. Process for the preparation of the compounds of formula (Ia):

(Ia) by condensation of an organometallic derivative of formula (XV) with a radical electrophile Ar2-X '+ according to the diagram:

1) Ar2-X '+
2) H2O

(XV) (Ia) in which :

* R1, R2, R3, Y, Ar1, Ar2, W and n are defined according to claim 1;
* M1 represents a metal chosen from lithium, sodium, magnesium, zinc, titanium, tin, copper, boron or silicon and is preferably lithium;
* Ar2-X 'is an electrophilic radical generated by a compound chosen in particular among:
a halide or an aralkyl sulfate of formula Ar2-R12-L
in which :
- R12 represents an aliphatic chain of 1 to 6 atoms of carbon, linear or branched, saturated or unsaturated optionally substituted by a halogen or a group alkoxy or an oxo radical; and - L is defined according to claim 7;
- a carbonyl compound of formula:
in which :
- p = 0 or 1;
- R13 represents the hydrogen atom, a C1-C6 group alkyl, halogen, alkoxy, aryloxy, or dialkylamino;
-a chloroformate of formula:

an isocyanate or an isothiocyanate of formula:
Ar2- (R12) pN = C = Q
in which Q represents the oxygen or sulfur atom ;
- a sulfonyl halide of formula:

in which Hal represents a halogen atom, preferably the chlorine atom;
-an epoxide of formula:

in which R10 and R'10 are defined according to the claim 1;
* X has the same meaning as X '. 14. Compounds useful in particular as intermediates in the preparation of the compounds according to claim 1, characterized in that they meet formulas IIIa, IIIb, IV, VII, XIII, XIX, XX, XXII, XXIV and XXVII:

(IIIa) (IIIb) (IV) (VII) (XIII) (XIX) (XX) (XXII) (XXIV) (XXVII) in which :
- RE is defined according to claim 8, - Z 'represents the oxygen, sulfur atom or the group N-R14, in which R14 represents the hydrogen atom or a C1-C6 alkyl group.
- the other groups are defined according to claim 1;

as well as the optical isomers of these compounds, in particular the enantiomers compounds comprising the asymmetric carbon carrying R1. 15. Compounds according to claim 2, characterized in that that they correspond to formula I in which simultaneously:
- R1 is a methyl radical;
- R2 is a methyl or ethyl radical;
- R3 represents a phenyl or pyridyl radical;
- R4 is a hydrogen atom or a formyl radical;
- R5 is a halogen atom or a C1-C3 alkyl or C1-C3 radical haloalkyl; and - W is an oxygen atom. 16. Compounds according to claim 3, characterized in that that they correspond to formula I in which simultaneously:
- R1 is a methyl radical;
- R2 is a methyl or ethyl radical;
- R3 represents a phenyl or pyridyl radical;
- R4 is a hydrogen atom or a formyl radical;
- R5 is a halogen atom or a C1-C3 alkyl or C1-C3 radical haloalkyl; and - W is an oxygen atom. 17. Fungicidal compositions, containing as active material (s) a (or more) compound according to claim 1, 2, 3, 4, 15 or 16, solid or liquid supports, acceptable in agriculture and surfactants active also acceptable in agriculture. 18. Fungicidal compositions according to claim 17, characterized in what they contain from 0.05 to 95% (by weight) of active ingredients. 19. Process for treating cultivated, affected or susceptible plants to be affected by fungal diseases, characterized in that an effective dose of a compound according to the aerial parts of these plants is applied claim 1, 2, 3, 4, 15 or 16. 20. Treatment method according to claim 19, characterized in that the effective dose is between 0.002 and 5 kg / ha, preferably between 0.005 and 1 kg / ha.